S-Allylmercaptocysteine induces G2/M phase arrest and apoptosis via ROS-mediated p38 and JNK signaling pathway in human colon cancer cells in vitro and in vivo

Xiaosong Zhu; Xiaoyan Jiang; Chonggang Duan; Ang Li; Yueyue Sun; Qiuchen Qi; Yan Liu; Siying Li; Zhongxi Zhao

doi:10.1039/C7RA10346H

S-Allylmercaptocysteine induces G2/M phase arrest and apoptosis via ROS-mediated p38 and JNK signaling pathway in human colon cancer cells in vitro and in vivo†

Xiaosong Zhu,^a Xiaoyan Jiang,^c Chonggang Duan,^d Ang Li,^a Yueyue Sun,^a Qiuchen Qi,^a Yan Liu,^a Siying Li*^a and Zhongxi Zhao

*^ab

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* Corresponding authors

^a School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, P. R. China
E-mail: zxzhao@sdu.edu.cn, uszxzhao@gmail.com, li-siying@hotmail.com
Fax: +86-531-88382548
Tel: +86-531-88382187

^b Shandong Provincial Key Laboratory of Mucosal and Transdermal Drug Delivery Technologies, Shandong Academy of Pharmaceutical Sciences, 989 Xinluo Street, Jinan, Shandong 250101, P. R. China

^c Department of Pharmacy, Qilu Hospital of Shandong University, 107 West Wenhua Road, Jinan 250012, China

^d Shandong Key Laboratory of Chemical Drugs, Shandong Academy of Pharmaceutical Sciences, Jinan 250101, China

Abstract

S-Allylmercaptocysteine (SAMC), a water-soluble organosulfur garlic derivative, has exhibited potential antitumor activity in various malignancies. Here we explored the effects of SAMC on colon cancer in vitro and in vivo and further elucidated the underlying molecule mechanisms. In this study, we found that SAMC potently suppressed cell viability and induced G2/M phase arrest and apoptosis in colon cancer HCT116 cells. Further studies showed that reactive oxygen species (ROS) attributed to SAMC-induced cell cycle arrest and apoptosis, which was attenuated by N-acetyl cysteine (NAC), an ROS scavenger. Moreover, we found that SAMC activated p38 and c-Jun N-terminal kinase (JNK) signal pathway, which was also blocked by NAC. Finally, SAMC administration in mice effectively delayed the growth of HCT116 xenografts without signs of toxicity. In conclusion, SAMC induced cell cycle G2/M phase arrest and apoptosis via ROS-mediated p38 and JNK signaling pathway in colon cancer HCT116 cells. In light of these results, SAMC may be a promising agent for anticancer therapy against colon cancer.

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DOI: https://doi.org/10.1039/C7RA10346H
Article type: Paper
Submitted: 18 Sep 2017
Accepted: 07 Oct 2017
First published: 20 Oct 2017
This article is Open Access

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RSC Adv., 2017,7, 49151-49158

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S-Allylmercaptocysteine induces G2/M phase arrest and apoptosis via ROS-mediated p38 and JNK signaling pathway in human colon cancer cells in vitro and in vivo

X. Zhu, X. Jiang, C. Duan, A. Li, Y. Sun, Q. Qi, Y. Liu, S. Li and Z. Zhao, RSC Adv., 2017, 7, 49151 DOI: 10.1039/C7RA10346H

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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S-Allylmercaptocysteine induces G2/M phase arrest and apoptosis via ROS-mediated p38 and JNK signaling pathway in human colon cancer cells in vitro and in vivo†

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S-Allylmercaptocysteine induces G2/M phase arrest and apoptosis via ROS-mediated p38 and JNK signaling pathway in human colon cancer cells in vitro and in vivo

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