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Food Chem Toxicol. 2016 Nov;97:336-345. doi: 10.1016/j.fct.2016.09.028. Epub 2016 Sep 28.

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

Author information

1
Department of Medical Laboratory Science and Biotechnology, School of Medicine and Health Sciences, Fooyin University, Kaohsiung, Taiwan; Aging and Disease Prevention Research Center, Fooyin University, Kaohsiung, Taiwan; Department of Education and Research, Fooyin University Hospital, Pingtung, Taiwan.
2
Yen Nien Biotechnology Co., Ltd., Taiwan.
3
Department of Medical Laboratory Science and Biotechnology, School of Medicine and Health Sciences, Fooyin University, Kaohsiung, Taiwan.
4
Department of Pathology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
5
Department of Molecular Biology and Human Genetics, College of Life Science, Tzu-Chi University, Hualien, Taiwan.
6
Department of Medical Laboratory Science and Biotechnology, School of Medicine and Health Sciences, Fooyin University, Kaohsiung, Taiwan; Department of Education and Research, Fooyin University Hospital, Pingtung, Taiwan; Department of Laboratory Medicine, Fooyin University Hospital, Pingtung, Taiwan.
7
Department of Recreation and Health Care Management, Chia Nan University of Pharmacy & Science, Tainan, Taiwan.
8
Department of Medical Laboratory Science and Biotechnology, School of Medicine and Health Sciences, Fooyin University, Kaohsiung, Taiwan. Electronic address: sc096@fy.edu.tw.

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.

KEYWORDS:

Apoptosis; Benzyl isothiocyanate; DNA damage; Oral squamous cell carcinoma; Redox stress

PMID:
27693243
DOI:
10.1016/j.fct.2016.09.028
[Indexed for MEDLINE]

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