Farnesiferol A from Ferula persica and Galbanic Acid from Ferula szowitsiana Inhibit P-Glycoprotein-Mediated Rhodamine Efflux in Breast Cancer Cell Lines.
Planta Med. 2011 Apr 11. Epub 2011 Apr 11. PMID: 21484672
Biotechnology Research Center and School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
In multidrug resistance (MDR), cancer cells exposed to anticancer agents develop resistance to a wide variety of chemicals and chemotherapeutic agents. Sesquiterpene coumarins are reported to inhibit P-glycoprotein and/or increase cytotoxicity of anticancer drugs in P-gp-overexpressing cell lines. In the current study, we investigated the effects of galbanic acid (from the roots of FERULA SZOWITSIANA) and farnesiferol A (from the roots of FERULA PERSICA) on functionality of the drug transporter P-glycoprotein (P-gp) using a rhodamine 123 efflux assay in a doxorubicin resistant breast cancer cell line (MCF7/Adr). Compared to verapamil, the well-known inhibitor of P-gp, galbanic acid (5, 10, and 25µg/mL), significantly inhibited the P-gp activity. In inhibition of the P-gp transporter, farnesiferol A (0.5 µg/mL) was more potent than verapamil at 15 min exposure. Our results indicate that the plant derived sesquiterpene coumarins, farnesiferol A and galbanic acid, may be promising candidatesto be considered for further studies on the reversal of multidrug resistance phenotype in chemotherapy of cancer patients.