title: Ganoderma lucidum derived ganoderenic acid B reverses ABCB1-mediated multidrug resistance in HepG2/ADM cells.
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.
authors.affiliation: College of Pharmacy, Jinan University, Guangzhou 510632, P.R. China.
authors.forename: Dao-Lu
authors.initials: DL
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Jinan University, Guangzhou 510632, P.R. China.
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Biosample Repository, Core Facility, Fox Chase Cancer Center, Philadelphia, PA, USA.
authors.forename: Dong-Hua
authors.initials: DH
authors.lastname: Yang
authors.affiliation: College of Pharmacy, Jinan University, Guangzhou 510632, P.R. China.
authors.forename: Chen-Ran
authors.initials: CR
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Jinan University, Guangzhou 510632, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: College of Pharmacy, Jinan University, Guangzhou 510632, P.R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Yao
authors.affiliation: College of Pharmacy, Jinan University, Guangzhou 510632, P.R. China.
authors.forename: Xiao-Qi
authors.initials: XQ
authors.lastname: Zhang
authors.affiliation: College of Pharmacy and Health Sciences, St. John's University, Queens, NY, USA.
authors.forename: Zhe-Sheng
authors.initials: ZS
authors.lastname: Chen
authors.affiliation: College of Pharmacy, Jinan University, Guangzhou 510632, P.R. China.
authors.forename: Wen-Cai
authors.initials: WC
authors.lastname: Ye
authors.affiliation: College of Pharmacy, Jinan University, Guangzhou 510632, P.R. China.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Zhang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology*; D020940:Reishi / Q000737:chemistry*; D013261:Sterols / Q000494:pharmacology*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D011134:Polysaccharides; D013261:Sterols; C476673:ganoderic acid B