B-Cell Lymphoma-2 Over-Expression Protects δ-Elemene-Induced Apoptosis in Human Lung Carcinoma Mucoepidermoid Cells via a Nuclear Factor Kappa B-Related Pathway
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概要
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δ-Elemene, an antitumor component, is a chemical compound isolated from Curcuma wenyujin, a Chinese traditional herb. We examined whether δ-elemene could affect apoptosis in human lung carcinoma mucoepidermoid NCI-H292 cells, and test whether and how the over-expression of B-cell lymphoma-2 (Bcl-2) and B-cell lymphoma extra large (Bcl-xL) could off-set the effect of δ-elemene on cell growth. The result demonstrated that δ-elemene significantly induced apoptosis of NCI-H292, as shown by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, DNA fragmentation measurement, Annexin V (AnV) binding of externalized phosphatidylserine and the mitochondrial probe JC-1 using flow cytometry. Treatment of NCI-H292 with δ-elemene increased both p38 mitogen-activated protein kinase (MAPK) and inducible nitric oxide synthese (iNOS) levels, suggesting these two molecules maybe relate to the apoptotic effect of δ-elemene. The cells with Bcl-2 or Bcl-xL over-expression showed an elevation of nuclear factor kappa B (NF-kappa B) activity, accompanying a significant reduction of δ-elemene-induced apoptosis. Furthermore, inhibition of NF-kappa B by IkBαSR, which is a powerful inhibitor of NF-kappa B, restored the ability of δ-elemene to induce apoptosis in the cells transfected with Bcl-2. These data strongly indicated that the apoptotic effect of δ-elemene on NCI-H292 was closely associated with the activity of NF-kappa B, which was up-regulated by Bcl-2 and Bcl-xL. In conclusion, δ-elemene induced apoptosis in NCI-H292 cells. The apoptotic effect of δ-elemene could be significantly offset by over-expression of either Bcl-2 or Bcl-xL. Bcl-2 and Bcl-xL were able to increase the activity of NF-kappa B, which was a known anti-apoptotic molecule in human lung cancer cells.
著者
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Yang Wei
Dep. Of Pharmacology Shenyang Pharmaceutical Univ.
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YANG Wei
Center for Drug Non-clinical Research and Evaluation of Pharmaceutical Industrial Research Institute
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YING Jun
Center for Drug Non-clinical Research and Evaluation of Pharmaceutical Industrial Research Institute
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LI Karen
Prince of Wales Hospital, Chinese University of Hong Kong
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Xie Chun
The Sixth Affiliated Hospital, Sun Yat-Sen University
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Ni Qing
Center for Drug Non-clinical Research and Evaluation of Pharmaceutical Industrial Research Institute
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Pan Xue
College of Pharmacy, GuangDong Pharmaceutical University
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Dong Jin
Department of Chemical Pharmaceutics, Shenyang Pharmaceutical University
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Wang Xi
College of Pharmacy, GuangDong Pharmaceutical University
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YING Jun
Center for Drug Non-Clinical Research and Evaluation of Pharmaceutical Industrial Research Institute in Guangzhou
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YANG Wei
Center for Drug Non-Clinical Research and Evaluation of Pharmaceutical Industrial Research Institute in Guangzhou
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Ni Qing
Center for Drug Non-clinical Research and Evaluation of Pharmaceutical Industrial Research Institute in Guangzhou
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