Induction of Caspase-3-Dependent Apoptosis in Human Leukemia HL-60 Cells by .DELTA.-Elemene

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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 inhibit cell growth and cell cycle progression and induce apoptosis in human leukemia HL-60 cells. The results demonstrated that δ-elemene induces significant apoptosis of HL-60 cells, as shown by MTT assay, annexin V (AnV) binding of externalized phosphatidylserine (PS), and the mitochondrial probe JC-1 using flow cytometry. HL-60 cells treated with δ-elemene showed high percentages in the early apoptotic and late apoptoctic/necrotic stages, as well as caspase-3 activation of HL-60 cells. By monitoring the changes in cell cycle profiles, we confirmed that δ-elemene could interfere with the cell cycle in the G2/M phase and induce apoptosis in HL-60 cells in a time-dependent manner. Caspase-3 plays a direct role in proteolytic cleavage of the cellular proteins responsible for progression to apoptosis. Therefore we examined apoptosis in HL-60 cells after exposure to δ-elemene and measured caspase-3 activities with or without Z-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk, a broad-spectrum caspase inhibitor) pretreatment using flow cytometric analysis. The results showed that δ-elemene could induce caspase-3 activation as detected by the decrease in δ-elemene-induced caspase-3 activities after treatment with z-VAD-fmk. In the present study, δ-elemene activated typical caspase-dependent apoptosis in HL-60 cells, as demonstrated by an inhibitory effect of z-VAD-fmk on this cell death. During δ-elemene-induced apoptosis, cytochrome c and apoptosis-inducing factor were released into the cytosol and BAX was translocated from the cytosol to mitochondria. However, these were not prevented by z-VAD-fmk. In conclusion, our study demonstrated that δ-elemene could induce G2/M cell cycle transition and trigger apoptosis through a caspase-3-dependent pathway.

著者

• YANG Wei

  Center for Drug Non-clinical Research and Evaluation of Pharmaceutical Industrial Research Institute

• YING Jun

  Center for Drug Non-clinical Research and Evaluation of Pharmaceutical Industrial Research Institute

• WANG Xi-Sha

  College of Pharmacy, Guang Dong Pharmaceutical University

• Dong Jin-hua

  Department Of Chemical Pharmaceutics Shenyang Pharmaceutical University

• XIE Chun-Ying

  Sixth Affiliated Hospital, Sun Yat-Sen University

• NI Qin-Chun

  Center for Drug Non-Clinical Research and Evaluation of Pharmaceutical Industrial Research Institute in Guangzhou

• PAN Xue-Diao

  College of Pharmacy, Guang dong Pharmaceutical University

• LIU Zhi-Min

  Prince of Wales Hospital, Chinese University of Hong Kong

• YING Jun

  Center for Drug Non-Clinical Research and Evaluation of Pharmaceutical Industrial Research Institute in Guangzhou

関連論文

• Cell Apoptosis Induced by δ-Elemene in Colorectal Adenocarcinoma Cells via a Mitochondrial-mediated Pathway
• The Effect of δ-Elemene on Hela Cell Lines by Apoptosis Induction
• 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
• Induction of Caspase-3-Dependent Apoptosis in Human Leukemia HL-60 Cells by .DELTA.-Elemene

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