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J Toxicol Sci. 2019;44(2):73-81. doi: 10.2131/jts.44.73.

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.

Author information

1
Division of Pathology, National Institute of Health Sciences.
2
Division of Toxicology, Department of Pharmacology, Toxicology and Therapeutics, School of Pharmacy, Showa University.
3
Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University.
4
Kyoto Institute of Japanese Diet Culture, Kyoto Prefectural University.

Abstract

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 ┬ÁM) 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.

KEYWORDS:

4-Methylthio-3-butenyl isothiocyanate (MTBITC); Apoptosis; Chemoprevention; Esophageal cancer cells; G2/M cell cycle arrest

PMID:
30726813
DOI:
10.2131/jts.44.73
[Indexed for MEDLINE]
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