Eupafolin,a flavonoid isolated from Artemisia princeps,induced apoptosis in human cervical adenocarcinoma HeLa cells |
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Authors: | Kyung‐Sook Chung Jung‐Hye Choi Nam‐In Back Myung‐Sook Choi Eun‐Kyung Kang Hae‐Gon Chung Tae‐Sook Jeong Kyung‐Tae Lee |
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Affiliation: | 1. Department of Biomedical Science, College of Medical Science, Kyung‐Hee University, Seoul, South Korea;2. Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung‐Hee University, Seoul, South Korea;3. Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung‐Hee University, Seoul, South Korea;4. Graduate School of Biotechnology and Plant Metabolism Research Center, Kyung‐Hee University, Suwon, South Korea;5. Department of Food Science and Nutrition, Kyungpook National University, Daegu, South Korea;6. GangHwa Agricultural R&D Center, Incheon, South Korea;7. National Research Laboratory of Lipid Metabolism, Atherosclerosis, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea |
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Abstract: | Although eupafolin, a flavone found in Artemisia princeps Pampanini, has been shown to inhibit the growth of several human cancer cells, its mode of action is poorly understood. In this study, we investigated the pro‐apoptotic activities of eupafolin in human cervical carcinoma HeLa cells. It was found that eupafolin induced apoptosis in a dose‐dependent manner, as evidenced by DNA fragmentation and the accumulation of positive cells for annexin V. In addition, eupafolin triggered the activations of caspases‐3, ‐6, ‐7, ‐8, and ‐9 and the cleavages of their substrates, such as, poly (ADP‐ribose) polymerase and lamin A/C. Furthermore, treatment with eupafolin resulted in a loss of mitochondrial membrane potential (ΔΨm), increased the release of cytochrome c to the cytosol, and altered the expression levels of B‐cell lymphoma 2 (Bcl‐2) family proteins. Interestingly, caspase‐8, an initiator caspase, was activated after the loss of ΔΨm and the activations of caspases‐3 and ‐9. Moreover, treatment with z‐DEVD‐fmk (a specific caspase‐3 inhibitor) and the overexpression of Bcl‐2 prevented eupafolin‐stimulated caspase‐8 activation. Altogether, these results suggest that the eupafolin‐induced apoptosis in HeLa cells is mediated by caspase‐dependent pathways, involving caspases‐3, ‐9, and ‐8, which are initiated by the Bcl‐2‐dependent loss of ΔΨm. |
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Keywords: | Apoptosis Bcl‐2 Caspase Eupafolin Mitochondria |
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