title: 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.affiliation: College of Pharmacy, Nankai University, Tianjin 300071, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lei
authors.forename: Juan
authors.initials: J
authors.lastname: Tan
authors.forename: Michael
authors.initials: M
authors.lastname: Wink
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Ma
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Guannan
authors.initials: G
authors.lastname: Su
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D031311:Corydalis / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000470:Alkaloids; D000970:Antineoplastic Agents; D007546:Isoquinolines; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010936:Plant Extracts; C039109:isoquinoline; C421109:multidrug resistance-associated protein 1