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Liu DL , Li YJ , Yang DH , Wang CR , Xu J , Yao N , Zhang XQ , Chen ZS , Ye WC , Zhang DM
Ganoderma lucidum derived ganoderenic acid B reverses ABCB1-mediated multidrug resistance in HepG2/ADM cells
Int J Oncol. 2015 May;46(5) :2029-38
PMID: 25779097 URL: https://www.ncbi.nlm.nih.gov/pubmed/25779097
AbstractChemotherapy is one of the most common therapeutic option for metastatic tumors and hematological malignancies. ABCB1-mediated multidrug resistance is the major obstacle for chemotherapy. Natural products with diversified structures are ideal source of ABCB1 modulators. Ganoderenic acid B, a lanostane-type triterpene isolated from Ganoderma lucidum, exhibited potent reversal effect on ABCB1-mediated multidrug resistance of HepG2/ADM cells to doxorubicin, vincristine and paclitaxel. Similarly, ganoderenic acid B could also significantly reverse the resistance of ABCB1-overexpressing MCF-7/ADR cells to doxorubicin. Furthermore, ganoderenic acid B notably enhanced intracellular accumulation of rhodamine-123 in HepG2/ADM cells through inhibition of its efflux. ABCB1 siRNA interference assay indicated that the reversal activity of ganoderenic acid B was dependent on ABCB1. Further mechanistic investigations found that ganoderenic acid B did not alter the expression level of ABCB1 and the activity of ABCB1 ATPase. Molecular docking model displayed that the positions of ganoderenic acid B binding to ABCB1 were different from the region of verapamil interacted with ABCB1. Collectively, ganoderenic acid B can enhance the cytotoxicity of chemotherapeutics towards ABCB1-mediated MDR cancer cells via inhibition of the transport function of ABCB1. These findings provide evidence that ganoderenic acid B has the potential to be developed into an ABCB1-mediated multidrug resistance reversal agent.
NotesLiu, Dao-Lu Li, Ying-Jie Yang, Dong-Hua Wang, Chen-Ran Xu, Jun Yao, Nan Zhang, Xiao-Qi Chen, Zhe-Sheng Ye, Wen-Cai Zhang, Dong-Mei Greece Int J Oncol. 2015 May;46(5):2029-38. doi: 10.3892/ijo.2015.2925. Epub 2015 Mar 12.