Farnesiferol A from Ferula persica and galbanic acid from Ferula szowitsiana inhibit P-glycoprotein-mediated rhodamine efflux in breast cancer cell lines.

Abstract

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.

• Authors: Mohammad Yahya Hanafi-Bojd, Mehrdad Iranshahi, Fatemeh Mosaffa, Shahireh Omidvar Tehrani, Fatemeh Kalalinia, Javad Behravan
• Journal: Planta medica (Planta Med) Vol. 77 Issue 14 Pg. 1590-3 (Sep 2011) ISSN: 1439-0221 [Electronic] Germany
• PMID: 21484672 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Georg Thieme Verlag KG Stuttgart · New York.

Chemical References

• ATP Binding Cassette Transporter, Subfamily B
• Antineoplastic Agents
• Coumarins
• Plant Extracts
• Sesquiterpenes
• Rhodamine 123
• farnesiferol A
• galbanic acid
• Verapamil

Topics

• ATP Binding Cassette Transporter, Subfamily B (drug effects, metabolism)
• Antineoplastic Agents (chemistry, pharmacology)
• Biological Transport
• Cell Line, Tumor
• Coumarins (chemistry, pharmacology)
• Drug Resistance, Neoplasm
• Female
• Ferula (chemistry)
• Humans
• Plant Extracts (chemistry)
• Plant Roots (chemistry)
• Rhodamine 123 (metabolism)
• Sesquiterpenes (chemistry, pharmacology)
• Verapamil (pharmacology)