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

  • Int J Oncol. 2015 May;46(5):2029-38. doi: 10.3892/ijo.2015.2925.
Dao-Lu Liu  1 ,  Ying-Jie Li  1 ,  Dong-Hua Yang  2 ,  Chen-Ran Wang  1 ,  Jun Xu  1 ,  Nan Yao  1 ,  Xiao-Qi Zhang  1 ,  Zhe-Sheng Chen  3 ,  Wen-Cai Ye  1 ,  Dong-Mei Zhang  1
Affiliations
  • 1. College of Pharmacy, Jinan University, Guangzhou 510632, P.R. China.
  • 2. Biosample Repository, Core Facility, Fox Chase Cancer Center, Philadelphia, PA, USA.
  • 3. College of Pharmacy and Health Sciences, St. John's University, Queens, NY, USA.
PMID: 25779097 DOI: 10.3892/ijo.2015.2925
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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