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

• Hirata Tadashi

  Division of Pathology, National Institute of Health Sciences Division of Toxicology, Department of Pharmacology, Toxicology and Therapeutics, School of Pharmacy, Showa University

• Cho Young-Man

  Division of Pathology, National Institute of Health Sciences

• Suzuki Isamu

  Division of Pathology, National Institute of Health Sciences Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University

• Toyoda Takeshi

  Division of Pathology, National Institute of Health Sciences

• Akagi Jun-ichi

  Division of Pathology, National Institute of Health Sciences

• Nakamura Yasushi

  Kyoto Institute of Japanese Diet Culture, Kyoto Prefectural University

• Numazawa Satoshi

  Division of Toxicology, Department of Pharmacology, Toxicology and Therapeutics, School of Pharmacy, Showa University

• Ogawa Kumiko

  Division of Pathology, National Institute of Health Sciences

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 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.

Journal

• The Journal of Toxicological Sciences

  The Journal of Toxicological Sciences 44 (2), 73-81, 2019

  The Japanese Society of Toxicology

Keywords

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

Details

• CRID: 1390845713050620288
• NII Article ID: 130007590638
• NII Book ID: AN00002808
• DOI: 10.2131/jts.44.73
• ISSN: 18803989
• ISSN: 03881350
• NDL BIB ID: 029707348
• PubMed: 30726813
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I029707348
• Web Site: https://www.jstage.jst.go.jp/article/jts/44/2/44_73/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2020013393
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed