An isoquinoline alkaloid from the Chinese herbal plant Corydalis yanhusuo W.T. Wang inhibits P-glycoprotein and multidrug resistance-associate protein 1.

Abstract

Overexpression of P-glycoprotein (P-gp) and multidrug resistance-associate protein 1 (MRP1) is a major mechanism leading to multidrug resistance (MDR) of cancer cells. These transporters expel anti-cancer drugs and greatly impair therapeutic efficacy of chemotherapy. A Chinese herbal plant Yanhusuo (Corydalis yanhusuo W.T. Wang, YHS) is frequently used in functional food and traditional Chinese medicine to improve the efficacy of chemotherapy. The objective of this work was to study effects of glaucine, an alkaloid component of YHS, on P-gp and MRP1 in resistant cancer cells. The resistant cancer cell line, MCF-7/ADR and corresponding parental sensitive cells were employed to determine reversal properties of glaucine. Glaucine inhibits P-gp and MRP1-mediated efflux and activates ATPase activities of the transporters, indicating that it is a substrate and inhibits P-gp and MRP1 competitively. Furthermore, glaucine suppresses expression of ABC transporter genes. It reverses the resistance of MCF-7/ADR to adriamycin and mitoxantrone effectively.

• Authors: Yu Lei, Juan Tan, Michael Wink, Yonggang Ma, Na Li, Guannan Su
• Journal: Food chemistry (Food Chem) Vol. 136 Issue 3-4 Pg. 1117-21 (Feb 15 2013) ISSN: 1873-7072 [Electronic] England
• PMID: 23194502 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Alkaloids
• Antineoplastic Agents
• Isoquinolines
• Multidrug Resistance-Associated Proteins
• Plant Extracts
• isoquinoline
• multidrug resistance-associated protein 1

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (antagonists & inhibitors, metabolism)
• Alkaloids (pharmacology)
• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Corydalis (chemistry)
• Drug Resistance, Neoplasm
• Humans
• Isoquinolines (pharmacology)
• Multidrug Resistance-Associated Proteins (antagonists & inhibitors, metabolism)
• Neoplasms (drug therapy, genetics, metabolism)
• Plant Extracts (pharmacology)