Benzyl isothiocyanate promotes apoptosis of oral cancer cells via an acute redox stress-mediated DNA damage response

Yao Tsung Yeh, Yen Nien Hsu, Sheng Yun Huang, Jian Sheng Lin, Zi Feng Chen, Nan Haw Chow, Shu Hui Su, Huey Wen Shyu, Ching Chiang Lin, Wu Tein Huang, Hua Yeh, Yu chia chih, Yu Hsuan Huang, Shu Jem Su

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Benzyl isothiocyanate (BITC) is a cruciferous vegetable-derived compound with anticancer properties in human cancer cells. However, its anticancer potential and underlying mechanisms remain absent in human oral cancer cells. Results indicate that BITC inhibits growth, promotes G2/M phase arrest and triggers apoptosis of OC2 cells with a minimal toxicity to normal cells. BITC-induced cell death was completely prevented by pretreatment with thiol-containing redox compounds including N-acetyl-L-cysteine (NAC), glutathione (GSH), dithiothreitol, and 2-mercaptoethanol, but not free radical scavengers mito-TEMPO, catalase, apocynin, L-NAME and mannitol. BITC rapidly produced reactive oxygen species and nitric oxide, triggered oxidative DNA damage. BITC effectively decreased the intracellular GSH and GSH/GSSG ratio and redox balance recovery by thiol-containing redox compounds, but not by free radical scavengers. Accordingly, redox stresses-DNA damage response (DDR) activated ATM, Chk2, p53, and p21 and subsequently resulted in G2/M phase arrest by inhibiting Cdc2 and cyclin B1. Notably, BITC-induced apoptosis was associated with reduced Mcl-1 and Bcl-2 expression, diminished mitochondrial membrane potential (ΔΨm), and increased PARP cleavage. These BITC-induced redox stress-mediated DDR and apoptosis could be blocked by NAC and GSH. Therefore, BITC can be a rational drug candidate for oral cancer and acted via a redox-dependent pathway.

Original languageEnglish
Pages (from-to)336-345
Number of pages10
JournalFood and Chemical Toxicology
Volume97
DOIs
Publication statusPublished - 2016 Nov 1

All Science Journal Classification (ASJC) codes

  • Food Science
  • Toxicology

Fingerprint Dive into the research topics of 'Benzyl isothiocyanate promotes apoptosis of oral cancer cells via an acute redox stress-mediated DNA damage response'. Together they form a unique fingerprint.

Cite this