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	Ye Zhang, Xiao-Dong Mu, En-Zhe Li, Ying Luo, Na Song, Xiu-Juan Qu, Xue-Jun Hu, Yun-Peng Liu
Journal	International journal of molecular sciences (Int J Mol Sci) Vol. 14 Issue 5 Pg. 10075-89 (May 10 2013) ISSN: 1422-0067 [Print] Switzerland
PMID	23665906 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	ATP Binding Cassette Transporter, Subfamily B, Member 1 Adaptor Proteins, Signal Transducing Antineoplastic Agents Sesquiterpenes beta-elemene Doxorubicin CBLB protein, human Proto-Oncogene Proteins c-cbl
Topics	ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism) Adaptor Proteins, Signal Transducing (metabolism) Animals Antineoplastic Agents (pharmacology, therapeutic use) Cell Line, Tumor Curcuma (chemistry) Doxorubicin (pharmacology, therapeutic use) Drug Resistance, Multiple (drug effects) Drug Resistance, Neoplasm (drug effects) Gastric Mucosa (metabolism) Humans Male Mice Mice, Inbred BALB C Mice, Nude Proto-Oncogene Proteins c-cbl (metabolism) Sesquiterpenes (pharmacology, therapeutic use) Signal Transduction (drug effects) Stomach (drug effects) Stomach Neoplasms (drug therapy, metabolism)

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