6‐Dehydrogingerdione,an active constituent of dietary ginger,induces cell cycle arrest and apoptosis through reactive oxygen species/c‐Jun N‐terminal kinase pathways in human breast cancer cells |
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Authors: | Ya‐Ling Hsu Chung‐Yi Chen Ming‐Feng Hou Eing‐Mei Tsai Yuh‐Jyh Jong Chih‐Hsing Hung Po‐Lin Kuo |
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Affiliation: | 1. Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;2. School of Medicine and Health Sciences, Fooyin University, Kaohsiung, Taiwan;3. Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan;4. Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan;5. Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;6. Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan;7. Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;8. Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan |
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Abstract: | This study is the first to investigate the anticancer effect of 6‐dehydrogingerdione (DGE), an active constituent of dietary ginger, in human breast cancer MDA‐MB‐231 and MCF‐7 cells. DGE exhibited effective cell growth inhibition by inducing cancer cells to undergo G2/M phase arrest and apoptosis. Blockade of cell cycle was associated with increased levels of p21, and reduced amounts of cyclin B1, cyclin A, Cdc2 and Cdc25C. DGE also enhanced the levels of inactivated phosphorylated Cdc2 and Cdc25C. DGE triggered the mitochondrial apoptotic pathway indicated by a change in Bax/Bcl‐2 ratios, resulting in caspase‐9 activation. We also found the generation of reactive oxygen species is a critical mediator in DGE‐induced cell growth inhibition. DGE clearly increased the activation of apoptosis signal‐regulating kinase 1 and c‐Jun N‐terminal kinase (JNK), but not extracellular signal‐regulated kinase 1/2 (ERK1/2) and p38. In addition, antioxidants vitamin C and catalase significantly decreased DGE‐mediated JNK activation and apoptosis. Moreover, blocking JNK by specific inhibitors suppressed DGE‐triggered mitochondrial apoptotic pathway. Taken together, these findings suggest that a critical role for reactive oxygen species and JNK in DGE‐mediated apoptosis of human breast cancer. |
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Keywords: | 6‐Dehydrogingerdione Apoptosis Cell cycle c‐Jun N‐terminal kinase Reactive oxygen species |
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