Sensitivity of allyl isothiocyanate to induce apoptosis via ER stress and the mitochondrial pathway upon ROS production in colorectal adenocarcinoma cells

Chiang,Jo‑Hua; Tsai,Fuu‑Jen; Hsu,Yuan‑Man; Yin,Mei‑Chin; Chiu,Hong‑Yi; Yang,Jai‑Sing

doi:10.3892/or.2020.7700

Sensitivity of allyl isothiocyanate to induce apoptosis via ER stress and the mitochondrial pathway upon ROS production in colorectal adenocarcinoma cells

Authors:
- Jo‑Hua Chiang
- Fuu‑Jen Tsai
- Yuan‑Man Hsu
- Mei‑Chin Yin
- Hong‑Yi Chiu
- Jai‑Sing Yang
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Affiliations: Department of Nursing, Chung‑Jen Junior College of Nursing, Health Sciences and Management, Chiayi County 62241, Taiwan, R.O.C., Human Genetics Center, Department of Medical Research, China Medical University Hospital, Taichung 40447, Taiwan, R.O.C., Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan, R.O.C., Department of Food Nutrition and Health Biotechnology, Asia University, Taichung 41354, Taiwan, R.O.C., Department of Pharmacy, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97002, Taiwan, R.O.C., Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40442, Taiwan, R.O.C.
Published online on: July 21, 2020 https://doi.org/10.3892/or.2020.7700
Pages: 1415-1424
Copyright: © Chiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Allyl isothiocyanate (AITC), a bioactive phytochemical compound that is a constituent of dietary cruciferous vegetables, possesses promising chemopreventive and anticancer effects. However, reports of AITC exerting antitumor effects on apoptosis induction of colorectal cancer (CRC) cells in vitro are not well elucidated. The present study focused on the functional mechanism of the endoplasmic reticulum (ER) stress‑based apoptotic machinery induced by AITC in human colorectal cancer HT‑29 cells. Our results indicated that AITC decreased cell growth and number, reduced viability, and facilitated morphological changes of apoptotic cell death. DNA analysis by flow cytometry showed G2/M phase arrest, and alterations in the modulated protein levels caused by AITC were detected via western blot analysis. AITC also triggered vital intrinsic apoptotic factors (caspase‑9/caspase‑3 activity), disrupted mitochondrial membrane potential, and stimulated mitochondrial‑related apoptotic molecules (e.g., cytochrome c, apoptotic protease activating factor 1, apoptosis‑inducing factor, and endonuclease G). Additionally, AITC prompted induced cytosolic Ca2+ release and Ca2+‑dependent ER stress‑related signals, such as calpain 1, activating transcription factor 6α, glucose‑regulated proteins 78 and 94, growth arrest‑ and DNA damage‑inducible protein 153 (GADD153), and caspase‑4. The level of reactive oxygen species (ROS) production was found to induce the hallmark of ER stress GADD153, proapoptotic marker caspase‑3, and calpain activity after AITC treatment. Our findings showed for the first time that AITC induced G2/M phase arrest and apoptotic death via ROS‑based ER stress and the intrinsic pathway (mitochondrial‑dependent) in HT‑29 cells. Overall, AITC may exert an epigenetic effect and is a potential bioactive compound for CRC treatment.

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