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

doi:10.1016/j.fct.2016.09.028

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Title:	Benzyl isothiocyanate promotes apoptosis of oral cancer cells via an acute redox stress-mediated DNA damage response
Authors:	Yeh, Yao-Tsung Hsu, Yen-Nien Huang, Sheng-Yun Lin, Jian-Sheng Chen, Zi-Feng Chow, Nan-Haw Su, Shu-Hui Shyu, Huey-Wen Lin, Ching-Chiang Huang, Wu-Tein Yeh, Hua Chih, Yu-chia Huang, Yu-Hsuan Su, Shu-Jem
Contributors:	Fooyin Univ, Sch Med & Hlth Sci, Dept Med Lab Sci & Biotechnol Fooyin Univ, Aging & Dis Prevent Res Ctr Fooyin Univ Hosp, Dept Educ & Res Yen Nien Biotechnol Co Ltd Natl Cheng Kung Univ, Coll Med, Dept Pathol Tzu Chi Univ, Coll Life Sci, Dept Mol Biol & Human Genet Fooyin Univ Hosp, Dept Lab Med Chia Nan Univ Pharm & Sci, Dept Recreat & Hlth Care Management
Keywords:	Benzyl isothiocyanate Oral squamous cell carcinoma DNA damage Apoptosis Redox stress
Date:	2016-11
Issue Date:	2018-01-18 11:38:42 (UTC+8)
Publisher:	Pergamon-Elsevier Science Ltd
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 G(2)/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 G(2)/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 (Delta Psi m), 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. (C) 2016 Elsevier Ltd. All rights reserved.
Relation:	Food and Chemical Toxicology, v.97, pp.336-345
Appears in Collections:	[Dept. of Recreation and Health-Care Management] Periodical Articles

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