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.
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.
Hsu
Ya-Ling
YL
Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Chen
Chung-Yi
CY
Hou
Ming-Feng
MF
Tsai
Eing-Mei
EM
Jong
Yuh-Jyh
YJ
Hung
Chih-Hsing
CH
Kuo
Po-Lin
PL
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005233:Fatty Alcohols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005260:Female; D020939:Zingiber officinale / Q000737:chemistry; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009994:Osmolar Concentration; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism*; D027343:Rhizome / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects*
C555348:6-dehydrogingerdione; D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D005233:Fatty Alcohols; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D006139:Guaiacol; D048031:JNK Mitogen-Activated Protein Kinases