Goniothalamin induces cell cycle-specific apoptosis by modulating the redox status in MDA-MB-231 cells
Journal
European Journal of Pharmacology
Journal Volume
522
Journal Issue
1-3
Pages
20-29
Date Issued
2005
Author(s)
CHE-MING TENG
Abstract
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 G2/M phase and apoptosis. By means of cell cycle synchronization, the G2/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 G2/M phase in MDA-MB-231 cells. ? 2005 Elsevier B.V. All rights reserved.
Subjects
Apoptosis; cdc25C; Goniothalamin; MDA-MB-231 cell; Redox status
SDGs
Other Subjects
acetylcysteine; antioxidant; buthionine sulfoximine; glutathione; goniothalenol; reactive oxygen metabolite; thiol; apoptosis; article; cancer cell culture; cell cycle; cell cycle G2 phase; cell line; controlled study; drug mechanism; human; human cell; mitosis; oxidation reduction reaction; priority journal; Antioxidants; Apoptosis; Blotting, Western; Buthionine Sulfoximine; cdc25 Phosphatase; Cell Cycle; Cell Cycle Proteins; Cell Line, Tumor; Cell Survival; Cytochromes c; Dimethyl Sulfoxide; Humans; Intracellular Membranes; Membrane Potentials; Mimosine; Mitochondria; Nocodazole; Oxidation-Reduction; Pyrones; Thymidine; Time Factors
Type
journal article