Natural agents’ role in cancer chemo-resistance prevention and treatment: molecular mechanisms and therapeutic prospects
Main Article Content
Keywords
anti-cancer, natural products, molecular
Abstract
Cancer is a leading cause of morbidity and mortality worldwide, necessitating exploring novel preventive and therapeutic strategies. Over the years, the potential of natural agents in cancer prevention and treatment has garnered considerable attention. This review highlights the current understanding of the molecular mechanical bases underlying the role of natural agents and their therapeutic potential in combating cancer. The molecular mechanisms through which these natural agents exert their anti-cancer activities are elucidated, encompassing modulation of signaling pathways involved in cell proliferation, apoptosis, angiogenesis, metastasis, and immune response. Additionally, the review delves into the emerging research on the epigenetic modifications induced by natural agents, providing a deeper insight into their anti-cancer properties.
References
2. Rueff J, Rodrigues AS. Cancer drug resistance: a brief overview from a genetic viewpoint. Cancer Drug Resistance. 2016;1395:1- 18. https://doi.org/10.1007/978-1-4939-3347-1_1
3. Nikolaou M, Pavlopoulou A, Georgakilas AG, Kyrodimos E. The challenge of drug resistance in cancer treatment: a current overview. Clinical & Experimental Metastasis. 2018;35(4):309-18.
4. Gottesman MM. Mechanisms of cancer drug resistance. Annual review of medicine. 2002;53(1):615-27.
5. Wang X, Zhang H, Chen X. Drug resistance and combating drug resistance in cancer. Cancer Drug Resist. 2019;2(2):141-60. https://doi.org/10.20517/cdr.2019.10
6. Daniel C, Bell C, Burton C, Harguindey S, Reshkin SJ, Rauch C. The role of proton dynamics in the development and maintenance of multidrug resistance in cancer. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2013;1832(5):606-17. https://doi.org/10.1016/j.bbadis.2013.01.020
7. Perez-Tomas R. Multidrug resistance: retrospect and prospects in anti-cancer drug treatment. Current medicinal chemistry. 2006;13(16):1859-76.
8. Choromanska A, Chwilkowska A, Kulbacka J, et al. Modifications of Plasma Membrane Organization in Cancer Cells for Targeted Therapy. Molecules. 2021;26(7):1850. https://doi.org/10.3390/molecules26071850
9. Guo Q, Cao H, Qi X, et al. Research progress in reversal of tumor multi-drug resistance via natural products. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents). 2017;17(11):1466-76.
10. Quagliano A, Gopalakrishnapillai A, Barwe SP. Understanding the mechanisms by which epigenetic modifiers avert therapy resistance in cancer. Frontiers in oncology. 2020;10:992.
11. Sevcikova A, Izoldova N, Stevurkova V, et al. The Impact of the Microbiome on Resistance to Cancer Treatment with Chemotherapeutic Agents and Immunotherapy. Int J Mol Sci. Jan 1 2022;23(1):488. https://doi.org/10.3390/ijms23010488
12. Dutta S, Mahalanobish S, Saha S, Ghosh S, Sil PC. Natural products: An upcoming therapeutic approach to cancer. Food and Chemical Toxicology. 2019;128:240-55.
13. Atanasov AG, Waltenberger B, Pferschy-Wenzig E-M, et al. Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnology advances. 2015;33(8):1582-1614.
14. Cragg GM, Newman DJ. Natural products: a continuing source of novel drug leads. Biochimica et Biophysica Acta (BBA)-General Subjects. 2013;1830(6):3670-95.
15. Alsayed AR, Hasoun LZ, Khader HA, Basheti IA, Permana AD. Bovine Colostrum Treatment of Specific Cancer Types: Current Evidence and Future Opportunities. Molecules. 2022;27(24):8641.
16. Ughachukwu P, Unekwe PJAom, research hs. Efflux Pump. Mediated Resistance in Chemotherapy. 2012;2(2):191-8.
17. Rang HP, Dale MM. Rang and Dale’s pharmacology. Elsevier Brasil; 2007.
18. Alfarouk KO, Stock C-M, Taylor S, et al. Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp. 2015;15(1):1-13.
19. Vadlapatla RK, Vadlapudi AD, Pal D, Mitra AKJCPD. Mechanisms of drug resistance in cancer chemotherapy: coordinated role and regulation of efflux transporters and metabolizing enzymes. 2013;19(40):7126-40.
20. Wu Q, Yang Z, Nie Y, Shi Y, Fan DJCl. Multi-drug resistance in cancer chemotherapeutics: mechanisms and lab approaches. 2014;347(2):159-66.
21. Xavier CPR, Belisario DC, Rebelo R, et al. The role of extracellular vesicles in the transfer of drug resistance competences to cancer cells. Drug Resist Updat. May 2022;62:100833. https://doi.org/10.1016/j.drup.2022.100833
22. Chen Z, Shi T, Zhang L, et al. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: a review of the past decade. 2016;370(1):153-64.
23. Dean M, Hamon Y, Chimini GJJolr. The human ATP-binding cassette (ABC) transporter superfamily. 2001;42(7):1007-17.
24. Giddings EL, Champagne DP, Wu MH, et al. Mitochondrial ATP fuels ABC transporter-mediated drug efflux in cancer chemoresistance. Nat Commun. 2021;12(1):2804. https://doi.org/10.1038/s41467-021-23071-6
25. Zhang J-TJCr. Use of arrays to investigate the contribution of ATP-binding cassette transporters to drug resistance in cancer chemotherapy and prediction of chemosensitivity. 2007;17(4):311-23.
26. Nikolaou M, Pavlopoulou A, Georgakilas AG, Kyrodimos EJC, Metastasis E. The challenge of drug resistance in cancer treatment: a current overview. 2018;35(4):309-18.
27. Fojo AT, Ueda K, Slamon DJ, Poplack D, Gottesman M, Pastan IJPotNAoS. Expression of a multidrug-resistance gene in human tumors and tissues. 1987;84(1):265-9.
28. Robinson K, Tiriveedhi VJFio. Perplexing role of P-glycoprotein in tumor microenvironment. 2020;10:265.
29. Marin JJG, Monte MJ, Macias RIR, et al. Expression of Chemoresistance-Associated ABC Proteins in Hepatobiliary, Pancreatic and Gastrointestinal Cancers. Cancers (Basel). 2022;14(14):3524. https://doi.org/10.3390/cancers14143524
30. Pishas KI, Cowley KJ, Pandey A, et al. Phenotypic Consequences of SLC25A40-ABCB1 Fusions beyond Drug Resistance in High- Grade Serous Ovarian Cancer. Cancers (Basel). 2021;13(22):5644. https://doi.org/10.3390/cancers13225644
31. Vaidyanathan A, Sawers L, Gannon A-L, et al. ABCB1 (MDR1) induction defines a common resistance mechanism in paclitaxeland olaparib-resistant ovarian cancer cells. 2016;115(4):431-41.
32. Satake K, Tsukamoto M, Mitani Y, et al. Human ABCB1 confers cells resistance to cytotoxic guanidine alkaloids from Pterogyne nitens. 2015;25(3):249-56.
33. Bukowski K, Kciuk M, Kontek R. Mechanisms of Multidrug Resistance in Cancer Chemotherapy. Int J Mol Sci. 2020;21(9):3233. https://doi.org/10.3390/ijms21093233
34. Amawi H, Sim H-M, Tiwari AK, Ambudkar SV, Shukla SJDTiDD, Effects, Toxicity. ABC transporter-mediated multidrug-resistant cancer. 2019:549-80.
35. Nobili S, Mini E, Riganti C. Multidrug resistance in Cancer: Pharmacological Strategies from Basic Research to Clinical Issues. Frontiers Media SA; 2015.
36. Rosenberg MF, Mao Q, Holzenburg A, Ford RC, Deeley RG, Cole SPJJoBC. The structure of the multidrug resistance protein 1 (MRP1/ABCC1): crystallization and single-particle analysis. 2001;276(19):16076-82.
37. Munoz M, Henderson M, Haber M, Norris MJIl. Role of the MRP1/ABCC1 multidrug transporter protein in cancer. 2007;59(12):752-7.
38. Cho S, Lu M, He X, et al. Notch1 regulates the expression of the multidrug resistance gene ABCC1/MRP1 in cultured cancer cells. 2011;108(51):20778-83.
39. Alatise KL, Gardner S, Alexander-Bryant A. Mechanisms of Drug Resistance in Ovarian Cancer and Associated Gene Targets. Cancers (Basel). 2022;14(24):6246. https://doi.org/10.3390/cancers14246246
40. Sosnik A, Bendayan R. Drug efflux pumps in cancer resistance pathways: from molecular recognition and characterization to possible inhibition strategies in chemotherapy. Academic Press; 2019.
41. Müller M, Meijer C, Zaman G, et al. Overexpression of the gene encoding the multidrug resistance-associated protein results in increased ATP-dependent glutathione S-conjugate transport. 1994;91(26):13033-7.
42. Mo W, Liu J-Y, Zhang J-TJRaicr, therapy. Elsevier A, The Netherlands. Biochemistry and pharmacology of human ABCC1/MRP1 and its role in detoxification and in multidrug resistance of cancer chemotherapy. 2012:371-404.
43. Delou JMA, Souza ASO, Souza LCM, Borges HL. Highlights in Resistance Mechanism Pathways for Combination Therapy. Cells. 2019;8(9):1013. https://doi.org/10.3390/cells8091013
44. Hanssen KM, Wheatley MS, Yu DMT, et al. GSH facilitates the binding and inhibitory activity of novel multidrug resistance protein 1 (MRP1) modulators. FEBS J. 2022;289(13):3854-75. https://doi.org/10.1111/febs.16374
45. Chang X-bJM-DRiC. Molecular mechanism of ATP-dependent solute transport by multidrug resistance-associated protein 1. 2010:223-249.
46. Burg D, Wielinga P, Zelcer N, Saeki T, Mulder GJ, Borst PJMp. Inhibition of the multidrug resistance protein 1 (MRP1) by peptidomimetic glutathione-conjugate analogs. 2002;62(5):1160-6.
47. Haider T, Pandey V, Banjare N, Gupta PN, Soni V. Drug resistance in cancer: mechanisms and tackling strategies. Pharmacol Rep. 2020;72(5):1125-51. https://doi.org/10.1007/s43440-020-00138-7
48. Mao Q, Unadkat JDJTAj. Role of the breast cancer resistance protein (BCRP/ABCG2) in drug transport—an update. 2015;17(1):65- 82.
49. Zheng Q, Zhang M, Zhou F, Zhang L, Meng X. The Breast Cancer Stem Cells Traits and Drug Resistance. Front Pharmacol. 2020;11:599965. https://doi.org/10.3389/fphar.2020.599965
50. Ma L, Liu T, Jin Y, Wei J, Yang Y, Zhang HJTB. ABCG2 is required for self-renewal and chemoresistance of CD133-positive human colorectal cancer cells. 2016;37(9):12889-96.
51. Lei X, He Q, Li Z, et al. Cancer stem cells in colorectal cancer and the association with chemotherapy resistance. Med Oncol. 2021;38(4):43. https://doi.org/10.1007/s12032-021-01488-9
52. Horsey AJ, Cox MH, Sarwat S, Kerr IDJBST. The multidrug transporter ABCG2: still more questions than answers. 2016;44(3):824- 30.
53. Mo W, Zhang J-TJIjob, biology m. Human ABCG2: structure, function, and its role in multidrug resistance. 2012;3(1):1.
54. Vaidya FU, Sufiyan Chhipa A, Mishra V, et al. Molecular and cellular paradigms of multidrug resistance in cancer. Cancer Rep (Hoboken). 2022;5(12):e1291. https://doi.org/10.1002/cnr2.1291
55. Pan ST, Li ZL, He ZX, et al. Molecular mechanisms for tumour resistance to chemotherapy. 2016;43(8):723-37.
56. Folmer Y, Schneider M, Blum H, Hafkemeyer PJCgt. Reversal of drug resistance of hepatocellular carcinoma cells by adenoviral delivery of anti-ABCC2 antisense constructs. 2007;14(11):875-84.
57. Costa AR, Duarte AC, Costa-Brito AR, Goncalves I, Santos CRA. Bitter taste signaling in cancer. Life Sci. 2023;315:121363. https://doi.org/10.1016/j.lfs.2022.121363
58. Balaji SA, Udupa N, Chamallamudi MR, Gupta V, Rangarajan AJPo. Role of the drug transporter ABCC3 in breast cancer chemoresistance. 2016;11(5):e0155013.
59. Chen Y, Zhou H, Yang S, Su DJCB, Function. Increased ABCC2 expression predicts cisplatin resistance in non‐small cell lung cancer. 2021;39(2):277-86.
60. Guengerich FPJCrit. Cytochrome p450 and chemical toxicology. 2008;21(1):70-83.
61. Guengerich FPJJob, toxicology m. Mechanisms of cytochrome P450 substrate oxidation: MiniReview. 2007;21(4):163-8.
62. Jančová P, Šiller MJTodm. Phase II drug metabolism. 2012:35-60.
63. Cummings J, Boyd G, Ethell BT, et al. Enhanced clearance of topoisomerase I inhibitors from human colon cancer cells by glucuronidation. 2002;63(4):607-13.
64. Meijerman I, Beijnen JH, Schellens JHJCtr. Combined action and regulation of phase II enzymes and multidrug resistance proteins in multidrug resistance in cancer. 2008;34(6):505-20.
65. Kaur G, Gupta SK, Singh P, Ali V, Kumar V, Verma M. Drug-metabolizing enzymes: role in drug resistance in cancer. Clin Transl Oncol. 2020;22(10):1667-80. https://doi.org/10.1007/s12094-020-02325-7
66. Liu Q, Liu Z, Hua W, Gou S. Discovery of 6-(7-Nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol Derivatives as Glutathione Transferase Inhibitors with Favorable Selectivity and Tolerated Toxicity. J Med Chem. 2021;64(3):1701-12. https://doi.org/10.1021/acs. jmedchem.0c02048
67. Joncourt F, Buser K, Altermatt H, Bacchi M, Oberli A, Cerny TJGo. Multiple drug resistance parameter expression in ovarian cancer. 1998;70(2):176-82.
68. Patel N, Chatterjee SK, Vrbanac V, et al. Rescue of paclitaxel sensitivity by repression of Prohibitin1 in drug-resistant cancer cells. 2010;107(6):2503-8.
69. Green J, Robertson L, Clark AJBjoc. Glutathione S-transferase expression in benign and malignant ovarian tumours. 1993;68(2):235-9.
70. Jardim BV, Moschetta MG, Leonel C, et al. Glutathione and glutathione peroxidase expression in breast cancer: an immunohistochemical and molecular study. 2013;30(3):1119-28.
71. Yu P, Du Y, Cheng X, Yu Q, Huang L, Dong RJWjoso. Expression of multidrug resistance-associated proteins and their relation to postoperative individualized chemotherapy in gastric cancer. 2014;12(1):1-6.
72. Ge J, Tian A-X, Wang Q-S, et al. The GSTP1 105Val allele increases breast cancer risk and aggressiveness but enhances response to cyclophosphamide chemotherapy in North China. 2013;8(6):e67589.
73. Gautam P, Feroz Z, Tiwari S, Vijayraghavalu S, Shukla GC, Kumar M. Investigating the Role of Glutathione S- Transferase Genes, Histopathological and Molecular Subtypes, Gene-Gene Interaction and Its Susceptibility to Breast Carcinoma in Ethnic North- Indian Population. Asian Pac J Cancer Prev. 2022;23(10):3481-90. https://doi.org/10.31557/APJCP.2022.23.10.3481
74. Wang H, Gao X, Zhang X, et al. Glutathione S-transferase gene polymorphisms are associated with an improved treatment response to cisplatin-based chemotherapy in patients with non-small cell lung Cancer (NSCLC): a meta-analysis. 2018;24:7482.
75. Pacholak LM, Amarante MK, Guembarovski RL, Watanabe MAE, Panis CJMBR. Polymorphisms in GSTT1 and GSTM1 genes as possible risk factors for susceptibility to breast cancer development and their influence in chemotherapy response: a systematic review. 2020;47(7):5495-5501.
76. Pfeffer CM, Singh ATJIjoms. Apoptosis: a target for anticancer therapy. 2018;19(2):448.
77. Xu JF, Wan Y, Tang F, et al. Emerging Significance of Ginsenosides as Potentially Reversal Agents of Chemoresistance in Cancer Therapy. Front Pharmacol. 2021;12:720474. https://doi.org/10.3389/fphar.2021.720474
78. Tummers B, Green DRJIr. Caspase‐8: regulating life and death. 2017;277(1):76-89.
79. Kim R, Tanabe K, Uchida Y, et al. Current status of the molecular mechanisms of anticancer drug-induced apoptosis. 2002;50(5):343-52.
80. Bai L, Wang SJArom. Targeting apoptosis pathways for new cancer therapeutics. 2014;65:139-55.
81. Li Y, Li Z. Potential Mechanism Underlying the Role of Mitochondria in Breast Cancer Drug Resistance and Its Related Treatment Prospects. Front Oncol. 2021;11:629614. https://doi.org/10.3389/fonc.2021.629614
82. Hassan M, Watari H, AbuAlmaaty A, Ohba Y, Sakuragi NJBri. Apoptosis and molecular targeting therapy in cancer. 2014;2014
83. Fu Z, Zhao PY, Yang XP, et al. Cannabidiol regulates apoptosis and autophagy in inflammation and cancer: A review. Front Pharmacol. 2023;14:1094020. https://doi.org/10.3389/fphar.2023.1094020
84. Warren CF, Wong-Brown MW, Bowden NAJCd, disease. BCL-2 family isoforms in apoptosis and cancer. 2019;10(3):1-12.
85. Mortenson M, Schlieman M, Virudalchalam S, Bold RJJoSR. Overexpression of BCL-2 results in activation of the AKT/NF-kB Cell survival pathway. 2003;114(2):302.
86. Buchholz TA, Davis DW, McConkey DJ, et al. Chemotherapy-induced apoptosis and Bcl-2 levels correlate with breast cancer response to chemotherapy. 2003;9(1):33-41.
87. Sjöström J, Blomqvist C, von Boguslawski K, et al. The predictive value of bcl-2, bax, bcl-xL, bag-1, fas, and fasL for chemotherapy response in advanced breast cancer. 2002;8(3):811-16.
88. Deng X, Kornblau SM, Ruvolo PP, May Jr WSJJM. Regulation of Bcl2 phosphorylation and potential significance for leukemic cell chemoresistance. 2000;2000(28):30-7.
89. Post SM, Ma H, Malaney P, et al. AXL/MERTK inhibitor ONO-7475 potently synergizes with venetoclax and overcomes venetoclax resistance to kill FLT3-ITD acute myeloid leukemia. Haematologica. 2022;107(6):1311-22. https://doi.org/10.3324/ haematol.2021.278369
90. Alam M, Ali S, Mohammad T, Hasan GM, Yadav DK, Hassan MI. B Cell Lymphoma 2: A Potential Therapeutic Target for Cancer Therapy. Int J Mol Sci. Sep 28 2021;22(19):10442. https://doi.org/10.3390/ijms221910442
91. Niero EL, Rocha-Sales B, Lauand C, et al. The multiple facets of drug resistance: one history, different approaches. 2014;33(1):1- 14.
92. Bukowski K, Kciuk M, Kontek RJIjoms. Mechanisms of multidrug resistance in cancer chemotherapy. 2020;21(9):3233.
93. Helleday T, Petermann E, Lundin C, Hodgson B, Sharma RAJNRC. DNA repair pathways as targets for cancer therapy. 2008;8(3):193-204.
94. Li LY, Guan YD, Chen XS, Yang JM, Cheng Y. DNA Repair Pathways in Cancer Therapy and Resistance. Front Pharmacol. 2020;11:629266. https://doi.org/10.3389/fphar.2020.629266
95. Chatterjee N, Walker GCJE, mutagenesis m. Mechanisms of DNA damage, repair, and mutagenesis. 2017;58(5):235-63.
96. Huang R, Zhou PK. DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy. Signal Transduct Target Ther. 2021;6(1):254. https://doi.org/10.1038/s41392-021-00648-7
97. Jones M, Beuron F, Borg A, et al. Cryo-EM structures of the XPF-ERCC1 endonuclease reveal how DNA-junction engagement disrupts an auto-inhibited conformation. 2020;11(1):1-14.
98. Youn C-K, Kim M-H, Cho H-J, et al. Oncogenic H-Ras up-regulates expression of ERCC1 to protect cells from platinum-based anticancer agents. 2004;64(14):4849-57.
99. Rocha CRR, Silva MM, Quinet A, Cabral-Neto JB, Menck CFMJC. DNA repair pathways and cisplatin resistance: an intimate relationship. 2018;73
100. Olaussen KA, Dunant A, Fouret P, et al. DNA repair by ERCC1 in non–small-cell lung cancer and cisplatin-based adjuvant chemotherapy. 2006;355(10):983-91.
101. Baiomy MAE, El Kashef WFJAPjocpA. ERCC1 expression in metastatic triple negative breast cancer patients treated with platinum-based chemotherapy. 2017;18(2):507.
102. Yu W, Zhang L, Wei Q, Shao AJFio. O6-methylguanine-DNA methyltransferase (MGMT): challenges and new opportunities in glioma chemotherapy. 2020;9:1547.
103. Dupont C, Armant DR, Brenner CA. Epigenetics: definition, mechanisms and clinical perspective. NIH Public Access. 2009:351.
104. Berger SL, Kouzarides T, Shiekhattar R, Shilatifard AJG, development. An operational definition of epigenetics. 2009;23(7):781- 3.
105. Bozzini N, Avnet S, Baldini N, Cortini M. Epigenetic Regulation Mediated by Sphingolipids in Cancer. International Journal of Molecular Sciences. 2023;24(6):5294.
106. Quagliano A, Gopalakrishnapillai A, Barwe SPJFio. Understanding the mechanisms by which epigenetic modifiers avert therapy resistance in cancer. 2020;10:992.
107. Jurkowska RZ, Jurkowski TP, Jeltsch AJC. Structure and function of mammalian DNA methyltransferases. 2011;12(2):206-222.
108. Mazloumi Z, Farahzadi R, Rafat A, et al. Effect of aberrant DNA methylation on cancer stem cell properties. Exp Mol Pathol. 2022;125:104757. https://doi.org/10.1016/j.yexmp.2022.104757
109. Zeller C, Dai W, Steele NL, et al. Candidate DNA methylation drivers of acquired cisplatin resistance in ovarian cancer identified by methylome and expression profiling. 2012;31(42):4567-76.
110. Deaton AM, Bird AJG, development. CpG islands and the regulation of transcription. 2011;25(10):1010-22.
111. Muller D, Gyorffy B. DNA methylation-based diagnostic, prognostic, and predictive biomarkers in colorectal cancer. Biochim Biophys Acta Rev Cancer. 2022;1877(3):188722. https://doi.org/10.1016/j.bbcan.2022.188722
112. Majchrzak-Celinska A, Warych A, Szoszkiewicz M. Novel Approaches to Epigenetic Therapies: From Drug Combinations to Epigenetic Editing. Genes (Basel). 2021;12(2):28. https://doi.org/10.3390/genes12020208
113. Sumarpo A, Ito K, Saiki Y, et al. Genetic and epigenetic aberrations of ABCB1 synergistically boost the acquisition of taxane resistance in esophageal squamous cancer cells. 2020;526(3):586-91.
114. Ohata Y, Shimada S, Akiyama Y, et al. Acquired resistance with epigenetic alterations under long-term antiangiogenic therapy for hepatocellular carcinoma. 2017;16(6):1155-65.
115. Bhatla T, Wang J, Morrison DJ, et al. Epigenetic reprogramming reverses the relapse-specific gene expression signature and restores chemosensitivity in childhood B-lymphoblastic leukemia. 2012;119(22):5201-10.
116. Kim SH, Kang BC, Seong D, et al. EPHA3 Contributes to Epigenetic Suppression of PTEN in Radioresistant Head and Neck Cancer. Biomolecules. 2021;11(4):599. https://doi.org/10.3390/biom11040599
117. Issa ME, Takhsha FS, Chirumamilla CS, Perez-Novo C, Berghe WV, Cuendet MJCE. Epigenetic strategies to reverse drug resistance in heterogeneous multiple myeloma. 2017;9(1):1-13.
118. Zhan Y, Li Y, Guan B, et al. Long non-coding RNA HNF1A-AS1 promotes proliferation and suppresses apoptosis of bladder cancer cells through upregulating Bcl-2. 2017;8(44):76656.
119. Wei J-W, Huang K, Yang C, Kang C-SJOr. Non-coding RNAs as regulators in epigenetics. 2017;37(1):3-9.
120. O’Brien J, Hayder H, Zayed Y, Peng CJFie. Overview of microRNA biogenesis, mechanisms of actions, and circulation. 2018;9:402.
121. Tang JY, Chuang YT, Shiau JP, et al. Long Noncoding RNAs and Circular RNAs Regulate AKT and Its Effectors to Control Cell Functions of Cancer Cells. Cells. 2022;11(19):2940. https://doi.org/10.3390/cells11192940
122. Ling H, Fabbri M, Calin GAJNrDd. MicroRNAs and other non-coding RNAs as targets for anticancer drug development. 2013;12(11):847-65.
123. Arun G, Diermeier SD, Spector DLJTimm. Therapeutic targeting of long non-coding RNAs in cancer. 2018;24(3):257-.
124. Xie W, Chu M, Song G, et al. Emerging roles of long noncoding RNAs in chemoresistance of pancreatic cancer. Semin Cancer Biol. 2022;83:303-18. https://doi.org/10.1016/j.semcancer.2020.11.004
125. Liberti MV, Locasale JWJTibs. The Warburg effect: how does it benefit cancer cells? 2016;41(3):211-218.
126. Schwartz L, T Supuran C, O Alfarouk KJA-CAiMC. The Warburg effect and the hallmarks of cancer. 2017;17(2):164-170.
127. Vander Heiden MG, Cantley LC, Thompson CBJs. Understanding the Warburg effect: the metabolic requirements of cell proliferation. 2009;324(5930):1029-33.
128. Zhou Y, Tozzi F, Chen J, et al. Intracellular ATP levels are a pivotal determinant of chemoresistance in colon cancer cells. 2012;72(1):304-14.
129. Schneider V, Krieger ML, Bendas G, Jaehde U, Kalayda GVJJJoBIC. Contribution of intracellular ATP to cisplatin resistance of tumor cells. 2013;18(2):165-174.
130. Cao Y, Chen E, Wang X, Song J, Zhang H, Chen X. An emerging master inducer and regulator for epithelial-mesenchymal transition and tumor metastasis: extracellular and intracellular ATP and its molecular functions and therapeutic potential. Cancer Cell Int. 2023;23(1):20. https://doi.org/10.1186/s12935-023-02859-0
131. Zhang H, Steed A, Co M, Chen X. Cancer stem cells, epithelial-mesenchymal transition, ATP and their roles in drug resistance in cancer. Cancer Drug Resist. 2021;4(3):684-709. https://doi.org/10.20517/cdr.2021.32
132. Wang X, Li Y, Qian Y, et al. Extracellular ATP, as an energy and phosphorylating molecule, induces different types of drug resistances in cancer cells through ATP internalization and intracellular ATP level increase. 2017;8(50):87860.
133. Wilhelm K, Ganesan J, Müller T, et al. Graft-versus-host disease is enhanced by extracellular ATP activating P2X 7 R. 2010;16(12):1434.
134. Qian Y, Wang X, Li Y, Cao Y, Chen XJMCR. Extracellular ATP a new player in cancer metabolism: NSCLC cells internalize ATP in vitro and in vivo using multiple endocytic mechanisms. 2016;14(11):1087-96.
135. Song J, Qian Y, Evers M, Nielsen CM, Chen X. Cancer Stem Cell Formation Induced and Regulated by Extracellular ATP and Stanniocalcin-1 in Human Lung Cancer Cells and Tumors. Int J Mol Sci. 2022;23(23):14770. https://doi.org/10.3390/ ijms232314770
136. Xiao F, Li J, Huang K, et al. Macropinocytosis: mechanism and targeted therapy in cancers. Am J Cancer Res. 2021;11(1):14-30. 137. Du Z, Lovly CMJMc. Mechanisms of receptor tyrosine kinase activation in cancer. 2018;17(1):1-13.
138. Yoganathan S, Alagaratnam A, Acharekar N, Kong JJC. Ellagic Acid and Schisandrins: Natural Biaryl Polyphenols with Therapeutic Potential to Overcome Multidrug Resistance in Cancer. 2021;10(2):458.
139. Wang Z, Xie C, Huang Y, Lam CWK, Chow MSJPr. Overcoming chemotherapy resistance with herbal medicines: past, present and future perspectives. 2014;13(1):323-37.
140. Guo Q, Li X, Cui M-N, et al. CD13-A key player in multi-drug resistance in cancer chemotherapy. 2020.
141. Kita DH, Guragossian N, Zattoni IF, et al. Mechanistic basis of breast cancer resistance protein inhibition by new indeno [1, 2-b] indoles. 2021;11(1):1-16.
142. To KK, Wu X, Yin C, et al. Reversal of multidrug resistance by Marsdenia tenacissima and its main active ingredients polyoxypregnanes.J Ethnopharmacol. 2017;203:110-19. https://doi.org/10.1016/j.jep.2017.03.051
143. Rodríguez-Chávez JL, Mendez-Cuesta CA, Ramirez-Apan T, et al. Chemo-sensitizing activity of natural cadinanes from Heterotheca inuloides in human uterine sarcoma cells and their in silico interaction with ABC transporters. 2019;91:103091.
144. Gote V, Nookala AR, Bolla PK, Pal DJIjoms. Drug Resistance in Metastatic Breast Cancer: Tumor Targeted Nanomedicine to the Rescue. 2021;22(9):4673.
145. Guo Q, Cao H, Qi X, et al. Research progress in reversal of tumor multi-drug resistance via natural products. 2017;17(11):1466- 76.
146. Yuan R, Hou Y, Sun W, et al. Natural products to prevent drug resistance in cancer chemotherapy: a review. 2017;1401(1):19- 27.
147. Chang Y-T, Wang CC, Wang J-Y, et al. Tenulin and isotenulin inhibit P-glycoprotein function and overcome multidrug resistance in cancer cells. 2019;53:252-62.
148. Hano M, Tomášová L, Šereš M, Pavlíková L, Breier A, Sulová ZJM. Interplay between P-glycoprotein expression and resistance to endoplasmic reticulum stressors. 2018;23(2):337.
149. Teng Y-N, Sheu M-J, Hsieh Y-W, Wang R-Y, Chiang Y-C, Hung C-CJP. β-carotene reverses multidrug resistant cancer cells by selectively modulating human P-glycoprotein function. 2016;23(3):316-23.
150. Waghray D, Zhang QJJomc. Inhibit or Evade Multidrug Resistance P-Glycoprotein in Cancer Treatment: Miniperspective. 2017;61(12):5108-21.
151. Dei S, Braconi L, Trezza A, et al. Modulation of the spacer in N, N-bis (alkanol) amine aryl ester heterodimers led to the discovery of a series of highly potent P-glycoprotein-based multidrug resistance (MDR) modulators. 2019;172:71-94.
152. Chang Y-T, Lin Y-C, Sun L, et al. Wilforine resensitizes multidrug resistant cancer cells via competitive inhibition of P-glycoprotein. 2020;71:153239.
153. Chen H-J, Chung Y-L, Li C-Y, et al. Taxifolin resensitizes multidrug resistance cancer cells via uncompetitive inhibition of P-glycoprotein function. Molecules. 2018;23(12):3055. https://doi.org/10.3390/molecules23123055
154. Umsumarng S, Pitchakarn P, Yodkeeree S, et al. Modulation of P-glycoprotein by Stemona alkaloids in human multidrug resistance leukemic cells and structural relationships. Phytomedicine. 2017;34:182-190.
155. Chang Y-T, Lin Y-C, Sun L, et al. Wilforine resensitizes multidrug resistant cancer cells via competitive inhibition of P-glycoprotein. Phytomedicine. 2020;71:153239.
156. Chang Y-T, Wang CCN, Wang J-Y, et al. Tenulin and isotenulin inhibit P-glycoprotein function and overcome multidrug resistance in cancer cells. Phytomedicine. 2019;53:252-262.
157. Li H, Krstin S, Wink M. Modulation of multidrug resistant in cancer cells by EGCG, tannic acid and curcumin. Phytomedicine. 2018;50:213-222.
158. Tang J, Ji H, Ren J, Li M, Zheng N, Wu L. Solid lipid nanoparticles with TPGS and Brij 78: a co-delivery vehicle of curcumin and piperine for reversing P-glycoprotein-mediated multidrug resistance in vitro. Oncology letters. 2017;13(1):389-95.
159. Teng Y-N, Wang CCN, Liao W-C, Lan Y-H, Hung C-C. Caffeic acid attenuates multi-drug resistance in cancer cells by inhibiting efflux function of human P-glycoprotein. Molecules. 2020;25(2):247.
160. Xu W, Xie S, Chen X, Pan S, Qian H, Zhu X. Effects of Quercetin on the Efficacy of Various Chemotherapeutic Drugs in Cervical Cancer Cells. Drug Des Devel Ther. 2021;15:577-88. https://doi.org/10.2147/DDDT.S291865
161. Khonkarn R, Daowtak K, Okonogi S. Chemotherapeutic efficacy enhancement in P-gp-Overexpressing cancer cells by flavonoidloaded polymeric micelles. Aaps Pharmscitech. 2020;21:1-12.
162. Shastrala K, Kalam S, Damerakonda K, et al. Synthesis, characterization, and pharmacological evaluation of some metal complexes of quercetin as P-gp inhibitors. Future Journal of Pharmaceutical Sciences. 2021;7(1):1-13.
163. Singh A, Patel SK, Kumar P, et al. Quercetin acts as a P-gp modulator via impeding signal transduction from nucleotide-binding domain to transmembrane domain. Journal of Biomolecular Structure and Dynamics. 2020:1-9.
164. Nair B, Anto RJ, Sabitha M, Nath LR. Kaempferol-Mediated Sensitization Enhances Chemotherapeutic Efficacy of Sorafenib Against Hepatocellular Carcinoma: An In Silico and In Vitro Approach. Advanced Pharmaceutical Bulletin. 2020;10(3):472.
165. Peng S, Wang J, Lu C, et al. Emodin enhances cisplatin sensitivity in non-small cell lung cancer through Pgp downregulation. Oncology Letters. 2021;21(3):1-1.
166. Teng X, Wang SY, Shi YQ, et al. The role of emodin on cisplatin resistance reversal of lung adenocarcinoma A549/DDP cell. Anticancer Drugs. 2021; ;32(9):939-49. https://doi.org/10.1097/cad.0000000000001086
167. Zhang Q, Feng Y, Kennedy DJC, Sciences ML. Multidrug-resistant cancer cells and cancer stem cells hijack cellular systems to circumvent systemic therapies, can natural products reverse this? 2017;74(5):777-801.
168. Hamed AR, Abdel-Azim NS, Shams KA, Hammouda FMJBotNRC. Targeting multidrug resistance in cancer by natural chemosensitizers. 2019;43(1):1-14.
169. Dallavalle S, Dobričić V, Lazzarato L, et al. Improvement of conventional anti-cancer drugs as new tools against multidrug resistant tumors. 2020;50:100682.
170. Syed SB, Arya H, Fu I-H, et al. Targeting P-glycoprotein: Investigation of piperine analogs for overcoming drug resistance in cancer. 2017;7(1):1-18.
171. Turrini E, Sestili P, Fimognari CJT. Overview of the Anticancer Potential of the “King of Spices” Piper nigrum and Its Main Constituent Piperine. 2020;12(12):747.
172. Zhang Z-L, Jiang Q-C, Wang S-RJBC. Schisandrin A reverses doxorubicin-resistant human breast cancer cell line by the inhibition of P65 and Stat3 phosphorylation. 2018;25(2):233-42.
173. Tinoush B, Shirdel I, Wink MJFiP. Phytochemicals: Potential Lead Molecules for MDR Reversal. 2020;11:832. https://doi. org/10.3389/fphar.2020.00832
174. Nabekura TJT. Overcoming multidrug resistance in human cancer cells by natural compounds. 2010;2(6):1207-24.
175. Zhang Y-K, Wang Y-J, Gupta P, Chen Z-SJTAj. Multidrug resistance proteins (MRPs) and cancer therapy. 2015;17(4):802-12.
176. El-Readi MZ, Eid S, Abdelghany AA, Al-Amoudi HS, Efferth T, Wink M. Resveratrol mediated cancer cell apoptosis, and modulation of multidrug resistance proteins and metabolic enzymes. Phytomedicine. 2019;55:269-81.
177. Krisnamurti DGB, Wanandi SI, Louisa M. Curcumin increases the sensitivity of breast cancer cells to tamoxifen by inhibiting MRP2 mrna expression of efflux transporter MRP2. International Journal of Applied Pharmaceutics. 2019:88-90.
178. Louisa M, Wardhani BW. Quercetin improves the efficacy of sorafenib in triple negative breast cancer cells through the modulation of drug efflux transporters expressions. International Journal of Applied Pharmaceutics. 2019:129-34.
179. Tang H, Zeng L, Wang J, et al. Reversal of 5-fluorouracil resistance by EGCG is mediate by inactivation of TFAP2A/VEGF signaling pathway and down-regulation of MDR-1 and P-gp expression in gastric cancer. Oncotarget. 2017;8(47):82842.
180. La X, Zhang L, Li Z, Li H, Yang Y. (−)-Epigallocatechin Gallate (EGCG) enhances the sensitivity of colorectal cancer cells to 5-FU by inhibiting GRP78/NF-κB/miR-155-5p/MDR1 pathway. Journal of agricultural and food chemistry. 2019;67(9):2510-2518.
181. Kawahara I, Nishikawa S, Yamamoto A, Kono Y, Fujita TJPr, perspectives. Assessment of contribution of BCRP to intestinal absorption of various drugs using portal‐systemic blood concentration difference model in mice. 2020;8(1):e00544.
182. Zhang Y-K, Zhang X-Y, Zhang G-N, et al. Selective reversal of BCRP-mediated MDR by VEGFR-2 inhibitor ZM323881. 2017;132:29- 37.
183. Hee Choi Y, Yu A-MJCpd. ABC transporters in multidrug resistance and pharmacokinetics, and strategies for drug development. 2014;20(5):793-807.
184. Chen L, Manautou JE, Rasmussen TP, Zhong X-bJAPSB. Development of precision medicine approaches based on interindividual variability of BCRP/ABCG2. 2019;9(4):659-74.
185. Mahmoud N, Saeed ME, Sugimoto Y, Klauck SM, Greten HJ, Efferth TJO. Cytotoxicity of nimbolide towards multidrug-resistant tumor cells and hypersensitivity via cellular metabolic modulation. 2018;9(87):35762.
186. Ding Y, He J, Huang J, et al. Harmine induces anticancer activity in breast cancer cells via targeting TAZ. International journal of oncology. 2019;54(6):1995-2004. https://doi.org/10.3892/ijo.2019.4777
187. Jaramillo AC, Saig FA, Cloos J, Jansen G, Peters GJJCDR. How to overcome ATP-binding cassette drug efflux transporter-mediated drug resistance? 2018;1(1):6-29.
188. Kulsoom B, Shamsi TS, Afsar NAJSr. Lung resistance-related protein (LRP) predicts favorable therapeutic outcome in Acute Myeloid Leukemia. 2019;9(1):1-11.
189. Tang YC, Zhang Y, Zhou J, et al. Ginsenoside Rg3 targets cancer stem cells and tumor angiogenesis to inhibit colorectal cancer progression in vivo. Int J Oncol. 2018;52(1):127-38. https://doi.org/10.3892/ijo.2017.4183
190. Nakhjavani M, Hardingham JE, Palethorpe HM, et al. Ginsenoside Rg3: Potential Molecular Targets and Therapeutic Indication in Metastatic Breast Cancer. Medicines (Basel). 2019;6(1):17. https://doi.org/10.3390/medicines6010017
191. Wang P, Yang HL, Yang YJ, Wang L, Lee SCJE-BC, Medicine A. Overcome cancer cell drug resistance using natural products. 2015;2015:767136. https://doi.org/10.1155/2015/767136
192. Tang XY, Tang YX, Xu P, Zhou HY, Han L. [Effect of Peimine on ERCC1 mRNA and LRP Expressions of A549/DDP Multidrug Resistance Cell Line]. Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine. 2015;35(12):1490-4.
193. Mackay HJ, Twelves CJ. Targeting the protein kinase C family: are we there yet? Nature Reviews Cancer. 2007;7(7):554-62.
194. Swannie HC, Kaye SB. Protein kinase C inhibitors. Current oncology reports. 2002;4(1):37-46.
195. Newton AC. Protein kinase C: structure, function, and regulation. Journal of biological chemistry. 1995;270:28495-8.
196. Nishizuka Y. Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science. 1992;258(5082):607- 14.
197. Isakov N. Protein kinase C (PKC) isoforms in cancer, tumor promotion and tumor suppression. Elsevier; 36-52.
198. Zhao L-J, Xu H, Qu J-W, Zhao W-Z, Zhao Y-B, Wang J-H. Modulation of drug resistance in ovarian cancer cells by inhibition of protein kinase C-alpha (PKC-α) with small interference RNA (siRNA) agents. Asian Pacific Journal of Cancer Prevention. 2012;13(8):3631-6.
199. Filomenko R, Poirson-Bichat F, Billerey C, et al. Atypical protein kinase C ζ as a target for chemosensitization of tumor cells. Cancer research. 2002;62(6):1815-21.
200. Gollapudi S, Patel K, Jain V, Gupta S. Protein kinase C isoforms in multidrug resistant P388/ADR cells: a possible role in daunorubicin transport. Cancer letters. 1992;62(1):69-75.
201. Nabha SM, Glaros S, Hong M, et al. Upregulation of PKC-δ contributes to antiestrogen resistance in mammary tumor cells. Oncogene. 2005;24(19):3166-76.
202. Fine RL, Chambers TC, Sachs CW. P‐glycoprotein, multidrug resistance and protein kinase C. Stem cells. 1996;14(1):47-55.
203. Cartee L, Kucera GL. Protein kinase C modulation and anticancer drug response. Cancer investigation. 2000;18(8):731-9.
204. Gschwendt M, Kittstein W, Marks F. Protein kinase C activation by phorbol esters: do cysteine-rich regions and pseudosubstrate motifs play a role? Trends in biochemical sciences. 1991;16:167-9.
205. Yang J-M, Chin K-V, Hait WN. Interaction of P-glycoprotein with protein kinase C in human multidrug resistant carcinoma cells. Cancer research. 1996;56(15):3490-4.
206. Conseil G, Perez-Victoria JM, Jault J-M, et al. Protein kinase C effectors bind to multidrug ABC transporters and inhibit their activity. Biochemistry. 2001;40(8):2564-71.
207. Roy M, Mukherjee S, Sarkar R, Biswas J. Curcumin sensitizes chemotherapeutic drugs via modulation of PKC, telomerase, NF-κB and HDAC in breast cancer. Therapeutic Delivery. 2011/10/01 2011;2(10):1275-93. https://doi.org/10.4155/tde.11.97
208. Maurya AK, Vinayak M. Anticarcinogenic action of quercetin by downregulation of phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) via induction of p53 in hepatocellular carcinoma (HepG2) cell line. Molecular Biology Reports. 2015;42(9):1419-9.
209. Russo M, Palumbo R, Mupo A, et al. Flavonoid quercetin sensitizes a CD95-resistant cell line to apoptosis by activating protein kinase Cα. Oncogene. 2003;22(21):3330-42. https://doi.org/10.1038/sj.onc.1206493
210. Pljesa-Ercegovac M, Savic-Radojevic A, Matic M, et al. Glutathione transferases: potential targets to overcome chemoresistance in solid tumors. International Journal of Molecular Sciences. 2018;19(12):3785.
211. O’Brien ML, Tew KD. Glutathione and related enzymes in multidrug resistance. European journal of cancer. 1996;32(6):967-78.
212. Singh RR, Reindl KM. Glutathione S-Transferases in Cancer. Antioxidants. 2021;10(5):701.
213. Bukowski K, Kciuk M, Kontek R. Mechanisms of multidrug resistance in cancer chemotherapy. International journal of molecular sciences. 2020;21(9):3233. https://doi.org/10.3390/ijms21093233
214. Osborne MJ, de Oliveira LC, Volpon L, Zahreddine HA, Borden KLB. Overcoming drug resistance through the development of selective inhibitors of UDP-glucuronosyltransferase enzymes. Journal of molecular biology. 2019;431(2):258-72.
215. Wu J, Henderson C, Feun L, et al. Phase II study of darinaparsin in patients with advanced hepatocellular carcinoma. Investigational new drugs. 2010;28(5):670-6.
216. Shen H, Kauvar L, Tew KD. Importance of glutathione and associated enzymes in drug response. Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics. 1997;9(6-7):295-302.
217. Al Fayi M, Alamri A, Rajagopalan P. IOX-101 Reverses Drug Resistance Through Suppression of Akt/mTOR/NF-κB Signaling in Cancer Stem Cell-Like, Sphere-Forming NSCLC Cell. Oncology research. 2020;28(2):177.
218. Du Y, Zheng Y, Yu CX, et al. The Mechanisms of Yu Ping Feng San in Tracking the Cisplatin-Resistance by Regulating ATPBinding Cassette Transporter and Glutathione S-Transferase in Lung Cancer Cells. Front Pharmacol. 2021;12:678126. https:// doi.org/10.3389/fphar.2021.678126
219. Li J, Ye T, Liu Y, et al. Transcriptional activation of Gstp1 by MEK/ERK signaling confers chemo-resistance to cisplatin in lung cancer stem cells. Frontiers in oncology. 2019;9:476.
220. Eid SY, Althubiti MA, Abdallah ME, Wink M, El-Readi MZ. The carotenoid fucoxanthin can sensitize multidrug resistant cancer cells to doxorubicin via induction of apoptosis, inhibition of multidrug resistance proteins and metabolic enzymes. Phytomedicine. 2020;77:153280.
221. Wang Z, Liang S, Lian X, et al. Identification of proteins responsible for adriamycin resistance in breast cancer cells using proteomics analysis. Scientific reports. 2015;5(1):1-11.
222. Yang M, Li Y, Shen X, et al. CLDN6 promotes chemoresistance through GSTP1 in human breast cancer. Journal of Experimental & Clinical Cancer Research. 2017;36(1):1-15.
223. Cheng S-Y, Chen N-F, Wen Z-H, et al. Glutathione S-Transferase M3 Is Associated with Glycolysis in Intrinsic Temozolomide- Resistant Glioblastoma Multiforme Cells. International Journal of Molecular Sciences. 2021;22(13):7080.
224. Fruehauf JP, Brem H, Brem S, et al. In vitro drug response and molecular markers associated with drug resistance in malignant gliomas. Clinical Cancer Research. 2006;12(15):4523-32.
225. Geng M, Wang L, Chen X, Cao R, Li P. The association between chemosensitivity and Pgp, GST-π and Topo II expression in gastric cancer. Diagnostic pathology. 2013;8(1):1-5.
226. Liu C-z, Liu W, Zheng Y, et al. PTEN and PDCD4 are Bona Fide Targets of microRNA-21 in Human Cholangiocarcinoma△. Chinese Medical Sciences Journal. 2012;27(2):65-72.
227. Keyvani‐Ghamsari S, Khorsandi K, Gul A. Curcumin effect on cancer cells’ multidrug resistance: an update. Phytotherapy Research. 2020;34(10):2534-56.
228. Andjelkovic T, Pesic M, Bankovic J, Tanic N, Markovic ID, Ruzdijic S. Synergistic effects of the purine analog sulfinosine and curcumin on the multidrug resistant human non-small cell lung carcinoma cell line (NCI-H460/R). Cancer biology & therapy. 2008;7(7):1024-32. https://doi.org/10.4161/cbt.7.7.6036
229. Depeille P, Cuq P, Passagne I, Evrard A, Vian L. Combined effects of GSTP1 and MRP1 in melanoma drug resistance. British journal of cancer. 2005;93(2):216-23.
230. Wang W, Sun Y-p, Huang X-z, et al. Emodin enhances sensitivity of gallbladder cancer cells to platinum drugs via glutathion depletion and MRP1 downregulation. Biochemical pharmacology. 2010;79(8):1134-40. 231. Chen Y-Y, Li J, Hu J-D, et al. Reversing effects of emodin on multidrug resistance in resistant HL-60/ADR cells. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2013;21(6):1413-22.
232. Ou B-n, Tang H-h, Zhang H-y, Liang G, Wei Y. Preliminary study of the mechanism of reversal effect of emodin in KBV200 cells in vitro [J]. Shandong Medical Journal. 2011;24
233. Majidinia M, Mirza‐Aghazadeh‐Attari M, Rahimi M, et al. Overcoming multidrug resistance in cancer: Recent progress in nanotechnology and new horizons. IUBMB life. 2020;72(5):855-71.
234. Alqarni MH, Foudah AI, Muharram MM, Labrou NE. The Interaction of the Flavonoid Fisetin with Human Glutathione Transferase A1-1. Metabolites. 2021;11(3):190.
235. Du Y, Zheng Y, Yu CX, et al. The mechanisms of Yu Ping Feng San in tracking the cisplatin-resistance by regulating ATP-binding cassette transporter and glutathione S-transferase in lung cancer cells. Front Pharmacol. 2021;12
236. Jin L, Xu M, Luo X-H, Zhu X-F. Stephania tetrandra and ginseng-containing Chinese herbal formulation NSENL reverses cisplatin resistance in lung cancer xenografts. The American journal of Chinese medicine. 2017;45(02):385-401.
237. Liu C-M, Kao C-L, Tseng Y-T, Lo Y-C, Chen C-Y. Ginger phytochemicals inhibit cell growth and modulate drug resistance factors in docetaxel resistant prostate cancer cell. Molecules. 2017;22(9):1477.
238. Wang B, Shen C, Li Y, et al. Oridonin overcomes the gemcitabine resistant PANC-1/Gem cells by regulating GST pi and LRP/1 ERK/JNK signalling. OncoTargets and therapy. 2019;12:5751-5765. https://doi.org/10.2147/ott.s208924
239. Martin LJ. Fucoxanthin and its metabolite fucoxanthinol in cancer prevention and treatment. Marine drugs. 2015;13(8):4784- 98.
240. Eid SY, El-Readi MZ, Wink M. Carotenoids reverse multidrug resistance in cancer cells by interfering with ABC-transporters. Phytomedicine. 2012;19(11):977-87.
241. Wang F, Lu C-H, Willner I. From cascaded catalytic nucleic acids to enzyme–DNA nanostructures: controlling reactivity, sensing, logic operations, and assembly of complex structures. Chemical reviews. 2014;114(5):2881-941.
242. Liu LF. DNA topoisomerase poisons as antitumor drugs. Annual review of biochemistry. 1989;58(1):351-75.
243. Ganguly A, Das B, Roy A, et al. Betulinic acid, a catalytic inhibitor of topoisomerase I, inhibits reactive oxygen species–mediated apoptotic topoisomerase I–DNA cleavable complex formation in prostate cancer cells but does not affect the process of cell death. Cancer research. 2007;67(24):11848-58.
244. Wink M. Molecular modes of action of cytotoxic alkaloids: from DNA intercalation, spindle poisoning, topoisomerase inhibition to apoptosis and multiple drug resistance. The Alkaloids: Chemistry and Biology. 2007;64:1-47.
245. El-Readi MZ, Al-Abd AM, Althubiti MA, et al. Multiple Molecular Mechanisms to Overcome Multidrug Resistance in Cancer by Natural Secondary Metabolites. Front Pharmacol. 2021;12:942.
246. Li T-K, Liu LF. Tumor cell death induced by topoisomerase-targeting drugs. Annual review of pharmacology and toxicology. 2001;41(1):53-77. https://doi.org/10.1146/annurev.pharmtox.41.1.53
247. Austin CA, Sng J-H, Patel S, Fisher LM. Novel HeLa topoisomerase II is the IIβ isoform: complete coding sequence and homology with other type II topoisomerases. Biochimica et Biophysica Acta (BBA)-Gene Structure and Expression. 1993;1172(3):283- 291.
248. Chen W, Qiu J, Shen Y. Topoisomerase IIα, rather than IIβ, is a promising target in development of anti-cancer drugs. Drug discoveries & therapeutics. 2012;6(5):230-237.
249. Woessner RD, Mattern MR, Mirabelli CK, Johnson RK, Drake FH. Proliferation-and cell cycle-dependent differences in expression of the 170 kilodalton and 180 kilodalton forms of topoisomerase II in NIH-3T3 cells. Cell growth & differentiation: the molecular biology journal of the American Association for Cancer Research. 1991;2(4):209-14.
250. Parchment RE, Pessina A. Topoisomerase I inhibitors and drug resistance. Cytotechnology. 1998;27(1):149-64.
251. Infante Lara L, Fenner S, Ratcliffe S, et al. Coupling the core of the anticancer drug etoposide to an oligonucleotide induces topoisomerase II-mediated cleavage at specific DNA sequences. Nucleic acids research. 2018;46(5):2218-33.
252. Ma Z, Hano Y, Nomura T, Chen Y. Novel quinazoline–quinoline alkaloids with cytotoxic and DNA topoisomerase II inhibitory activities. Bioorganic & medicinal chemistry letters. 2004;14(5):1193-6. https://doi.org/10.1016/j.bmcl.2003.12.048
253. Lin J-P, Lu H-F, Lee J-H, et al. (-)-Menthol Inhibits DNA Topoisomerases I, II α and β and Promotes NF-Î B expression in Human Gastric Cancer SNU-5 Cells. Anticancer research. 2005;25(3B):2069-74.
254. Makhey D, Gatto B, Yu C, Liu A, Liu LF, LaVoie EJ. Coralyne and related compounds as mammalian topoisomerase I and topoisomerase II poisons. Bioorganic & medicinal chemistry. 1996;4(6):781-91.
255. Meng W, Ze-Fa LIU, Hua T, Bao-An C. Application of alkaloids in reversing multidrug resistance in human cancers. Chinese journal of natural medicines. 2018;16(8):561-71.
256. Xue X, Qu X-J, Gao Z-H, et al. Riccardin D, a novel macrocyclic bisbibenzyl, induces apoptosis of human leukemia cells by targeting DNA topoisomerase II. Investigational new drugs. 2012;30(1):212-22.
257. Greco O, Marples B, Joiner MC, Scott SD. How to overcome (and exploit) tumor hypoxia for targeted gene therapy. Journal of cellular physiology. 2003;197(3):312-25.
258. Brown JM. Exploiting the hypoxic cancer cell: mechanisms and therapeutic strategies. Molecular medicine today. 2000;6(4):157- 162.
259. Liu L, Ning X, Sun L, et al. Hypoxia‐inducible factor‐1α contributes to hypoxia‐induced chemoresistance in gastric cancer. Cancer science. 2008;99(1):121-128.
260. Semenza GL. HIF-1: mediator of physiological and pathophysiological responses to hypoxia. Journal of applied physiology. 2000;
261. Huang LE, Gu J, Schau M, Bunn HF. Regulation of hypoxia-inducible factor 1α is mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway. Proceedings of the National Academy of Sciences. 1998;95(14):7987-92.
262. Xu S, Yu C, Ma X, et al. IL-6 promotes nuclear translocation of HIF-1α to aggravate chemoresistance of ovarian cancer cells. European Journal of Pharmacology. 2021;894:173817.
263. Jin X, Gong L, Peng Y, Li L, Liu G. Enhancer-bound Nrf2 licenses HIF-1α transcription under hypoxia to promote cisplatin resistance in hepatocellular carcinoma cells. Aging (Albany NY). 2021;13(1):364.
264. Fang X, Li S, Yu H, et al. Epidemiological, comorbidity factors with severity and prognosis of COVID-19: a systematic review and meta-analysis. Aging. 2020;12(13):12493-503. https://doi.org/10.18632/aging.103579
265. Lei-Tao SUN, Zhang L-Y, Fei-Yu S, Min-He S, Shan-Ming R. Jiedu Sangen decoction inhibits chemoresistance to 5-fluorouracil of colorectal cancer cells by suppressing glycolysis via PI3K/AKT/HIF-1α signaling pathway. Chinese Journal of Natural Medicines. 2021;19(2):143-152.
266. Stoeltzing O, McCarty MF, Wey JS, et al. Role of hypoxia-inducible factor 1α in gastric cancer cell growth, angiogenesis, and vessel maturation. Journal of the National Cancer Institute. 2004;96(12):946-56.
267. McMahon S, Grondin F, McDonald PP, Richard DE, Dubois CM. Hypoxia-enhanced expression of the proprotein convertase furin is mediated by hypoxia-inducible factor-1: impact on the bioactivation of proproteins. Journal of Biological Chemistry. 2005;280(8):6561-9.
268. Wang G, Xie G, Han L, et al. Involvement of hypoxia-inducible factor-1 alpha in the upregulation of P-glycoprotein in refractory epilepsy. Neuroreport. 2019;30(17):1191-6.
269. Lv Y, Zhao S, Han J, Zheng L, Yang Z, Zhao L. Hypoxia-inducible factor-1α induces multidrug resistance protein in colon cancer. OncoTargets and therapy. 2015;8:1941.
270. Wen Y, Zhao R-Q, Zhang Y-K, et al. Effect of Y6, an epigallocatechin gallate derivative, on reversing doxorubicin drug resistance in human hepatocellular carcinoma cells. Oncotarget. 2017;8(18):29760.
271. Kathawala RJ, Gupta P, Ashby Jr CR, Chen Z-S. The modulation of ABC transporter-mediated multidrug resistance in cancer: a review of the past decade. Drug resistance updates. 2015;18:1-17.
272. Parohan M, Yaghoubi S, Seraji A, Javanbakht MH, Sarraf P, Djalali M. Risk factors for mortality in patients with Coronavirus disease 2019 (COVID-19) infection: a systematic review and meta-analysis of observational studies. The aging male : the official journal of the International Society for the Study of the Aging Male. Jun 8 2020:1-9. https://doi.org/10.1080/1368553 8.2020.1774748
273. Hassan S, Peluso J, Chalhoub S, et al. Quercetin potentializes the respective cytotoxic activity of gemcitabine or doxorubicin on 3D culture of AsPC-1 or HepG2 cells, through the inhibition of HIF-1α and MDR1. PLOS ONE. 2020;15(10):e0240676. https:// doi.org/10.1371/journal.pone.0240676
274. Mitani T, Ito Y, Harada N, et al. Resveratrol Reduces the Hypoxia-Induced Resistance to Doxorubicin in Breast Cancer Cells. Journal of Nutritional Science and Vitaminology. 2014;60(2):122-128. https://doi.org/10.3177/jnsv.60.122
275. Zhang C, Deng J, Liu D, et al. Nuciferine inhibits proinflammatory cytokines via the PPARs in LPS-induced RAW264. 7 cells. Molecules. 2018;23(10):2723.
276. Li Z, Chen Y, An T, et al. Nuciferine inhibits the progression of glioblastoma by suppressing the SOX2-AKT/STAT3-Slug signaling pathway. Journal of Experimental & Clinical Cancer Research. 2019;38(1):1-15.
277. Shu G, Qiu Y, Hao J, Fu Q, Deng X. Nuciferine alleviates acute alcohol-induced liver injury in mice: Roles of suppressing hepatic oxidative stress and inflammation via modulating miR-144/Nrf2/HO-1 cascade. Journal of Functional Foods. 2019;58:105-113.
278. Liu R-M, Xu P, Chen Q, Feng S-l, Xie Y. A multiple-targets alkaloid nuciferine overcomes paclitaxel-induced drug resistance in vitro and in vivo. Phytomedicine. 2020;79:153342.
279. Xu T, Guo P, He Y, et al. Application of curcumin and its derivatives in tumor multidrug resistance. Phytotherapy Research. 2020;34(10):2438-58.
280. Costea T, Vlad OC, Miclea L-C, Ganea C, Szöllősi J, Mocanu M-M. Alleviation of multidrug resistance by flavonoid and nonflavonoid compounds in breast, lung, colorectal and prostate cancer. International journal of molecular sciences. 2020;21(2):401.
281. Talib WH, Alsayed AR, Barakat M, Abu-Taha MI, Mahmod AI. Targeting drug chemo-resistance in cancer using natural products. Biomedicines. 2021;9(10):1353. https://doi.org/10.3390/biomedicines9101353