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

• Published in: International journal of oncology Vol. 46; no. 5; pp. 2029 - 2038
• Main Authors: LIU, 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
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.05.2015; Spandidos Publications UK Ltd
• Subjects: ABC transporter; ABCB1; Acids; Antineoplastic Agents - pharmacology; Apoptosis; ATP Binding Cassette Transporter, Subfamily B - metabolism; Blotting, Western; Cancer therapies; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - metabolism; Cell cycle; Cell Line, Tumor; Chemotherapy; Drug resistance; Drug Resistance, Multiple - drug effects; Experiments; ganoderenic acid B; Hematology; HepG2/ADM; Humans; Lipids; Liver Neoplasms - drug therapy; Liver Neoplasms - metabolism; multidrug resistance; Multidrug resistant organisms; Polysaccharides - pharmacology; Reishi - chemistry; Sterols - pharmacology; Traditional Chinese medicine; Tumors
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.2015.2925

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.