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Int. J. Mol. Sci. 2013, 14(5), 10075-10089; doi:10.3390/ijms140510075
Article

The Role of E3 Ubiquitin Ligase Cbl Proteins in β-Elemene Reversing Multi-Drug Resistance of Human Gastric Adenocarcinoma Cells

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Received: 21 March 2013; in revised form: 27 April 2013 / Accepted: 3 May 2013 / Published: 10 May 2013
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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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.
Keywords: E3 ubiquitin ligase; β-elemene; multidrug resistance; PI3K/Akt E3 ubiquitin ligase; β-elemene; multidrug resistance; PI3K/Akt
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Zhang, Y.; Mu, X.-D.; Li, E.-Z.; Luo, Y.; Song, N.; Qu, X.-J.; Hu, X.-J.; Liu, Y.-P. The Role of E3 Ubiquitin Ligase Cbl Proteins in β-Elemene Reversing Multi-Drug Resistance of Human Gastric Adenocarcinoma Cells. Int. J. Mol. Sci. 2013, 14, 10075-10089.

AMA Style

Zhang Y, Mu X-D, Li E-Z, Luo Y, Song N, Qu X-J, Hu X-J, Liu Y-P. The Role of E3 Ubiquitin Ligase Cbl Proteins in β-Elemene Reversing Multi-Drug Resistance of Human Gastric Adenocarcinoma Cells. International Journal of Molecular Sciences. 2013; 14(5):10075-10089.

Chicago/Turabian Style

Zhang, Ye; Mu, Xiao-Dong; Li, En-Zhe; Luo, Ying; Song, Na; Qu, Xiu-Juan; Hu, Xue-Jun; Liu, Yun-Peng. 2013. "The Role of E3 Ubiquitin Ligase Cbl Proteins in β-Elemene Reversing Multi-Drug Resistance of Human Gastric Adenocarcinoma Cells." Int. J. Mol. Sci. 14, no. 5: 10075-10089.



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