AI Article Synopsis
- Multidrug resistance in cancer treatment, caused by the overexpression of P-glycoprotein, severely limits the effectiveness of chemotherapy.
- The study highlights O-(4-ethoxyl-butyl)-berbamine (EBB) as a promising agent that enhances the effectiveness of doxorubicin against drug-resistant cancer cells by blocking P-glycoprotein's function and reducing its expression.
- Co-treating cancer cells with EBB and doxorubicin leads to significant cell cycle arrest and increased cell death, indicating a strong potential for improving cancer chemotherapy outcomes.
Article 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 doxorubicin could strongly potentiate the antitumor activity of doxorubicin, thus may have significant clinical application in cancer chemotherapy.
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| http://dx.doi.org/10.1002/jps.22082 | DOI Listing |
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