Goniothalamin induces cell cycle-specific apoptosis by modulating the redox status in MDA-MB-231 cells.
Goniothalamin, a natural occurring styryl-lactone, is a novel compound with putative anticancer activities. In the present study, the mechanism of action of goniothalamin was further investigated in human breast cancer MDA-MB-231 cells. Goniothalamin treatment of cells significantly induced cell cycle arrest at G(2)/M phase and apoptosis. By means of cell cycle synchronization, the G(2)/M phase cells proved to be the most sensitive fraction to goniothalamin-induced apoptosis. Cells treated with goniothalamin revealed an increase in intracellular reactive oxygen species and a decrease in intracellular free thiol contents. The disruption of intracellular redox balance caused by goniothalamin was associated an enhancement of cdc25C degradation. Furthermore, the antioxidant N-acetylcysteine and the glutathione synthesis inhibitor dl-buthionine-(S, R)-sulfoximine, inhibited and enhanced, respectively, the effects of goniothalamin on cell cycle arrest and apoptosis. Taken together, our result demonstrates for the first time that goniothalamin disrupts intracellular redox balance and induces cdc25C degradation, which in turn causes cell cycle arrest and cell death maximally at G(2)/M phase in MDA-MB-231 cells.
Chen
Wen-Ying
WY
Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung City, Taiwan.
Wu
Chin-Chung
CC
Lan
Yu-Hsuan
YH
Chang
Fang-Rong
FR
Teng
Che-Ming
CM
Wu
Yang-Chang
YC
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D008898:Mimosine / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D015739:Nocodazole / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D011753:Pyrones / Q000494:pharmacology*; D013936:Thymidine / Q000494:pharmacology; D013997:Time Factors; D020687:cdc25 Phosphatases / Q000378:metabolism
D000975:Antioxidants; D018797:Cell Cycle Proteins; D011753:Pyrones; C103280:goniothalamin; D008898:Mimosine; D019328:Buthionine Sulfoximine; D045304:Cytochromes c; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases; D015739:Nocodazole; D013936:Thymidine; D004121:Dimethyl Sulfoxide