title: Degradation of P-glycoprotein by pristimerin contributes to overcoming ABCB1-mediated chemotherapeutic drug resistance in vitro.
abstract: ABCB1 (P-glycoprotein, ABCB1/MDR1) is one of the major members of the ABC transporters linked to MDR in cancer cells. In this study, we observed that pristimerin, a natural triterpenoid, potently decreased P-gp in a dose-dependent manner in both drug-resistant KBv200 and stable transfected HEK293/ABCB1 cell lines. Moreover, pristimerin also inhibited cell proliferation and induced apoptosis in both cell lines. Intriguingly, reverse transcription-PCR, real-time PCR and protein turn-over assay revealed that the decrease of P-gp was independent of mRNA level but primarily owing to its protein stability. Furthermore, immunofluorescence study with anti-P-gp antibody showed that pristimerin disturbed the subcellular distribution of P-gp with decreased location in the plasma membrane. Taken together, these data suggest that subcellular distribution of P-gp and subsequent downregulation by pristimerin contribute to overcoming ABCB1-mediated chemotherapeutic drug resistance. Our findings suggested inducing the decrease of P-gp membrane protein could be a new promising alternative therapeutic strategy in ABCB1-mediated MDR.
authors.affiliation: Institute of Respiratory and Occupational Diseases, Collaborative Innovation Center for Cancer, Shanxi Datong University, Datong, Shanxi 037009, P.R. China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-Sen University, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-Sen University, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-Sen University, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Xiao-Kun
authors.initials: XK
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-Sen University, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Chen
authors.affiliation: Institute of Respiratory and Occupational Diseases, Collaborative Innovation Center for Cancer, Shanxi Datong University, Datong, Shanxi 037009, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Institute of Respiratory and Occupational Diseases, Collaborative Innovation Center for Cancer, Shanxi Datong University, Datong, Shanxi 037009, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-Sen University, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Li-Wu
authors.initials: LW
authors.lastname: Fu
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D053978:Pentacyclic Triterpenes; D059748:Proteolysis / Q000187:drug effects*; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D004317:Doxorubicin; C050414:celastrol