Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.
Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, USA.
Mar Drugs. 2012 Oct;10(10):2312-2321. doi: 10.3390/md10102312. Epub 2012 Oct 19.
The resistance of tumor cells to a broad range of anticancer agents continues to be a problem for the success of cancer chemotherapy. Multidrug resistance (MDR) is due in part to three drug transporter proteins: ABCB1/P-glycoprotein (P-gp), ABCC1/multidrug resistance protein 1 (MRP1) and ABCG2/breast cancer resistance protein (BCRP). These transporters are part of the ATP-binding cassette (ABC) superfamily, whose members function as ATP-dependent drug-efflux pumps. Their activity can be blocked by various drugs such as verapamil (calcium channel blocker) and cyclosporin A (immunosuppressive agent), etc. These compounds are called MDR modulators or reversals. This review highlights several marine natural products with reversal effect on multidrug resistance in cancer, including agosterol A, ecteinascidin 743, sipholane triterpenoids, bryostatin 1, and welwitindolinones.
肿瘤细胞对多种抗癌药物的耐药性仍然是癌症化疗成功的一个问题。多药耐药性(MDR)部分归因于三种药物转运蛋白:ABCB1/ P -糖蛋白(P - gp)、ABCC1/多药耐药相关蛋白 1(MRP1)和 ABCG2/乳腺癌耐药蛋白(BCRP)。这些转运蛋白是 ATP 结合盒(ABC)超家族的一部分,其成员作为 ATP 依赖性药物外排泵发挥作用。它们的活性可以被各种药物阻断,如维拉帕米(钙通道阻滞剂)和环孢素 A(免疫抑制剂)等。这些化合物被称为多药耐药调节剂或逆转剂。本文综述了几种具有逆转肿瘤多药耐药性的海洋天然产物,包括 agosterol A、ecteinascidin 743、sipholane 三萜、bryostatin 1 和 welwitindolinones。