A novel calmodulin antagonist O-(4-ethoxyl-butyl)-berbamine overcomes multidrug resistance in drug-resistant MCF-7/ADR breast carcinoma cells

Journal of Pharmaceutical Sciences
Rong LiuDong-Sheng Xiong

Abstract

Multidrug resistance (MDR) mediated by the overexpression of the drug efflux protein P-glycoprotein is one of the major obstacles to successful cancer chemotherapy. The development of safe and effective MDR-reversing agents is an important approach to addressing this problem clinically. In this study, we evaluated the P-gp-modulatory potential of O-(4-ethoxyl-butyl)-berbamine (EBB), a novel calmodulin antagonist and derivative of bisbenzylisoquinoline alkaloid, which significantly improved the chemosensitivity of P-glycoprotein-mediated multidrug-resistant cells to doxorubicin compared with the efficacy of a conventional P-glycoprotein inhibitor, verapamil. EBB not only blocked the function of P-glycoprotein confirmed by the fact that EBB increased intracellular accumulation of rhodamine 123 and doxorubicin but also inhibited the expression of P-glycoprotein actualized by downregulating P-glycoprotein. Furthermore, our results showed that cotreatment with EBB and doxorubicin resulted in marked G(2)/M arrest and apoptosis of MCF-7/ADR cells, accompanied by down-regulation of the proteins cdc2/p34 and cyclin B1 and increased the levels of calcium ions. Taken together, these results suggest that cotreatment with EBB and doxorubici...Continue Reading

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Citations

Mar 13, 2014·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Xiaoli Jin, Yulian Wu
Nov 6, 2013·Biochimica Et Biophysica Acta·Martin W Berchtold, Antonio Villalobo
Sep 6, 2012·Journal of Zhejiang University. Science. B·Shailendra Kapoor
Apr 14, 2015·BioMed Research International·Paul J DavisShaker A Mousa
Aug 11, 2020·The Journal of International Medical Research·Yachun LiWanzhong Yin
Feb 9, 2017·The Journal of Biological Chemistry·Zhigang LiDavid B Sacks
Sep 9, 2017·Evidence-based Complementary and Alternative Medicine : ECAM·Feng JiaLinshan Fu

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