Farnesiferol A from Ferula persica and Galbanic Acid from Ferula szowitsiana Inhibit P-Glycoprotein-Mediated Rhodamine Efflux in Breast Cancer Cell Lines
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 25 µg/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 candidates to be considered for further studies on the reversal of multidrug resistance phenotype in chemotherapy of cancer patients.
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