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Abstract Title:

β-Elemene, a compound derived from Rhizoma zedoariae, reverses multidrug resistance mediated by the ABCB1 transporter.

Abstract Source:

Oncol Rep. 2014 Feb ;31(2):858-66. Epub 2013 Nov 27. PMID: 24284783

Abstract Author(s):

Hui-Qin Guo, Guan-Nan Zhang, Yi-Jun Wang, Yun-Kai Zhang, Kamlesh Sodani, Tanaji T Talele, Charles R Ashby, Zhe-Sheng Chen

Article Affiliation:

Hui-Qin Guo

Abstract:

In the present in vitro study, we examined the effect of the compoundβ-elemene on the response of KB-C2 cells overexpressing the ABCB1 transporter to specific antineoplastic compounds. The MTT assay was used to determine the effects of β-elemene in combination with other anticancer drugs on ABCB1-overexpressing cancer cell lines. Furthermore, we used [3H]-paclitaxel accumulation, efflux assay, immunofluorescence experiments, western blot assays and docking analysis to ascertain the mechanism of action of β-elemene. The incubation of KB-C2 cells overexpressing ABCB1 transporter with β-elemene (100 µM) significantly augmented the antineoplastic efficacy of colchicine, vinblastine and paclitaxel when compared to KB-C2 cells incubated with these drugs alone. In HEK293 cells overexpressing the ABCB1 transporter, β-elemene significantly increased the cytotoxicity of paclitaxel. In addition, 100 µM of β-elemene significantly increased the accumulation of[3H]-paclitaxel and this was due to a decrease in [3H]-paclitaxel efflux when compared to controls. The incubation of KB-C2 cells with β-elemene (100 µM) for 72 h did not significantly alter the expression of ABCB1 protein levels. Immunofluorescence experiments indicated that β-elemene did not significantly alter the subcellular localization of the ABCB1 transporter. Docking analysis indicated that β-elemene binds to the drug-binding site of ABCB1 transporter. Finally, β-elemene at 100 µM partially (~50%) increased the sensitivity of the BCRP-overexpressing cell line, NCI-H460/MX20, tomitoxantrone, but β-elemene did not significantly alter the resistance of MRP1-transfected HEK293/MRP1 cells to vincristine. Overall, our in vitro findings indicated that β-elemene potentiates the cytotoxic effects of various antineoplastic drugs in cell lines overexpressing the ABCB1 transporterand that this is due to the inhibition of the efflux component of the ABCB1 transporter.

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Sayer Ji
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