Ganoderma lucidum derived ganoderenic acid B reverses ABCB1-mediated multidrug resistance in HepG2/ADM cells

  • Authors:
    • Dao-Lu Liu
    • Ying-Jie Li
    • Dong-Hua Yang
    • Chen-Ran Wang
    • Jun Xu
    • Nan Yao
    • Xiao-Qi Zhang
    • Zhe-Sheng Chen
    • Wen-Cai Ye
    • Dong-Mei Zhang
  • View Affiliations

  • Published online on: March 12, 2015     https://doi.org/10.3892/ijo.2015.2925
  • Pages: 2029-2038
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Abstract

Chemotherapy 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.
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May-2015
Volume 46 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Liu D, Li Y, Yang D, Wang C, Xu J, Yao N, Zhang X, Chen Z, Ye W, Zhang D, Zhang D, et al: Ganoderma lucidum derived ganoderenic acid B reverses ABCB1-mediated multidrug resistance in HepG2/ADM cells. Int J Oncol 46: 2029-2038, 2015.
APA
Liu, D., Li, Y., Yang, D., Wang, C., Xu, J., Yao, N. ... Zhang, D. (2015). Ganoderma lucidum derived ganoderenic acid B reverses ABCB1-mediated multidrug resistance in HepG2/ADM cells. International Journal of Oncology, 46, 2029-2038. https://doi.org/10.3892/ijo.2015.2925
MLA
Liu, D., Li, Y., Yang, D., Wang, C., Xu, J., Yao, N., Zhang, X., Chen, Z., Ye, W., Zhang, D."Ganoderma lucidum derived ganoderenic acid B reverses ABCB1-mediated multidrug resistance in HepG2/ADM cells". International Journal of Oncology 46.5 (2015): 2029-2038.
Chicago
Liu, D., Li, Y., Yang, D., Wang, C., Xu, J., Yao, N., Zhang, X., Chen, Z., Ye, W., Zhang, D."Ganoderma lucidum derived ganoderenic acid B reverses ABCB1-mediated multidrug resistance in HepG2/ADM cells". International Journal of Oncology 46, no. 5 (2015): 2029-2038. https://doi.org/10.3892/ijo.2015.2925