The medicinal plants effects on the gene expression of cytochrome P450 and P-glycoprotein in cultured colon and breast cancer cell line

Abstract

Using herbs in the Arab world is becoming increasingly common. Hence, there is a potential for pharmacokinetic and pharmacodynamic herb-drug interactions. Cytochrome P450 (CYP) enzymes and efflux transporter such as P-glycoprotein (P-gp) are vulnerable to modulation by the multiple active constituents of herbs. To examine the effects of some herbal plants on the gene expression of CYP1A1 metabolizing enzyme and P-glycoprotein. In vitro approach using human breast cancer cell line MCF7 and human colon adenocarcinoma Caco2 cell line were used to evaluate the effects of ten herbal plants Paronychia argentea lam., Achillea bibersteni L., Teucrium polium L., Achillea santolina L., Arbutus andrachne L., Ruta graveolens L. Chrysanthemum coronarium L., Iles paraguariensis A.st., Catha edulis Forsk., and Anthemis palastina Boiss on the mRNA expression of CYP1A1 and P-gp. The toxicities of these plants on the cell lines were evaluated with tetrazolium dye MTT test. Only Catha edulis had shown anti-proliferative activity against MCF7, but not against Caco2. Paronychia argentea, Ruta graveolens and Catha edulis on MCF7 and Paronychia argentea, Arbutus andrachne,Chrysanthenum coronarium and Anthemis palastina on Caco2 observed induction of CYP1A1 with dose dependant manner. Variation between induction and inhibition were noticed with plant effects on P-gp expression. Paronychia argentea has shown dose dependant induction effect, Anthemis palastina induced P-gp at high concentrations, Whereas both Teucrium polium and Catha edulis inhibit P-gp at 100μg/ml. The overall results indicate a potential food-drug interaction, which definitely should be investigated further on animal and human kinetic models.