4-Methylthio-3-butenyl isothiocyanate (MTBITC) induced apoptotic cell death and G2/M cell cycle arrest via ROS production in human esophageal epithelial cancer cells

To investigate the chemopreventive mechanisms of 4-Methylthio-3-butenyl isothiocyanate (MTBITC), we analyzed cell viability, cell cycle distribution, and expression levels for cell cycle and apoptosis-related proteins in MTBITC-treated malignant esophageal KYSE510 cells, with and without the reactiv...

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Bibliographic Details
Published in:Journal of toxicological sciences 2019, Vol.44(2), pp.73-81
Main Authors: Hirata, Tadashi, Cho, Young-Man, Suzuki, Isamu, Toyoda, Takeshi, Akagi, Jun-ichi, Nakamura, Yasushi, Numazawa, Satoshi, Ogawa, Kumiko
Format: Article
Language:English
Subjects:
4-Methylthio-3-butenyl isothiocyanate (MTBITC)
Acetylcysteine
AKT protein
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
Cancer
Carcinogenesis
Carcinogens
Caspase
Caspase-3
Caspase-9
Cell cycle
Cell death
Cell Line, Tumor
Cell Survival - drug effects
Cell viability
Chemoprevention
CHK1 protein
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Esophageal cancer cells
Esophageal Neoplasms - drug therapy
Esophageal Neoplasms - metabolism
Esophagus
G2 Phase Cell Cycle Checkpoints - drug effects
G2/M cell cycle arrest
Humans
Isothiocyanate
Isothiocyanates - pharmacology
Mitochondria
Protein expression
Proteins
Reactive oxygen species
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Summary:To investigate the chemopreventive mechanisms of 4-Methylthio-3-butenyl isothiocyanate (MTBITC), we analyzed cell viability, cell cycle distribution, and expression levels for cell cycle and apoptosis-related proteins in MTBITC-treated malignant esophageal KYSE510 cells, with and without the reactive oxygen species (ROS) scavenger N-acethyl-L-Cysteine (NAC). MTBITC dose-dependently reduced cell viability and Bcl2 protein expression, while it induced cleavages of caspase-3, caspase-9, and PARP-1, suggesting that reduced cell viability occurred through the mitochondrial apoptotic pathway in KYSE510 cells. In cell cycle distribution analysis, MTBITC (20-40 µM) induced cell cycle arrest at G2/M phase. Furthermore, MTBITC induced Chk1 and Akt phosphorylations and decreased p27 protein expression. Both apoptotic- and cell cycle-related changes induced by MTBITC treatment were abolished by NAC. These results suggest that MTBITC has chemopreventive potential for esophageal carcinogenesis by elimination of cancer cells via induction of mitochondrial apoptotic cell death, G2/M cell cycle arrest, and ROS production.
ISSN:0388-1350
1880-3989
DOI:10.2131/jts.44.73