title: The role of E3 ubiquitin ligase Cbl proteins in β-elemene reversing multi-drug resistance of human gastric adenocarcinoma cells.
abstract: Recent studies indicate that β-elemene, a compound isolated from the Chinese herbal medicine Curcuma wenyujin, is capable of reversing tumor MDR, although the mechanism remains elusive. In this study, β-Elemene treatment markedly increased the intracellular accumulation of doxorubicin (DOX) and rhodamine 123 in both K562/DNR and SGC7901/ADR cells and significantly inhibited the expression of P-gp. Treatment of SGC7901/ADR cells with β-elemene led to downregulation of Akt phosphorylation and significant upregulation of the E3 ubiquitin ligases, c-Cbl and Cbl-b. Importantly, β-elemene significantly enhanced the anti-tumor activity of DOX in nude mice bearing SGC7901/ADR xenografts. Taken together, our results suggest that β-elemene may target P-gp-overexpressing leukemia and gastric cancer cells to enhance the efficacy of DOX treatment.
authors.affiliation: Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China. cmuhuxuejun@yahoo.cn.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Mu
authors.forename: En-Zhe
authors.initials: EZ
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Luo
authors.forename: Na
authors.initials: N
authors.lastname: Song
authors.forename: Xiu-Juan
authors.initials: XJ
authors.lastname: Qu
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Hu
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Liu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D030024:Curcuma / Q000737:chemistry; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use*; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism*; D012717:Sesquiterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D013270:Stomach / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D012717:Sesquiterpenes; C445979:beta-elemene; D004317:Doxorubicin; C492211:CBLB protein, human; D050721:Proto-Oncogene Proteins c-cbl