J Cancer 2022; 13(1):243-252. doi:10.7150/jca.65297 This issue

Research Paper

Shikonin induced Apoptosis Mediated by Endoplasmic Reticulum Stress in Colorectal Cancer Cells

Hui Qi1,2*, Xing Zhang1*, Huanhuan Liu2, Meng Han2, Xuzhen Tang2, Shulan Qu1, Xiaoyu Wang1✉, Yifu Yang1✉

1. Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China.
2. Oncology and Immunology BU, Research Service Division, WuXi Apptec, Shanghai, China.
*These authors contributed equally to this work.

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Qi H, Zhang X, Liu H, Han M, Tang X, Qu S, Wang X, Yang Y. Shikonin induced Apoptosis Mediated by Endoplasmic Reticulum Stress in Colorectal Cancer Cells. J Cancer 2022; 13(1):243-252. doi:10.7150/jca.65297. Available from https://www.jcancer.org/v13p0243.htm

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Graphic abstract

Shikonin is a naphthoquinone pigment isolated from the root of Lithospermum erythrorhizon, which has displayed potent anti-tumor properties. However, the effects of shikonin in colorectal cancer cells have not been yet fully investigated. In this study, we demonstrated that shikonin significantly inhibited the activity of colorectal cancer cells in a time- and dose-dependent manner. The flow cytometry and western blot results indicated that shikonin induced cell apoptosis by down-regulating BCL-2 and activating caspase-3/9 and the cleavage of PARP. The expression of BiP and the PERK/elF2α/ATF4/CHOP and IRE1α /JNK signaling pathways were upregulated after shikonin treatment. The pre-treatment with N-acetyl cysteine significantly reduced the cytotoxicity of shikonin. Taken together, shikonin could inhibit proliferation of the colorectal cancer cell through the activation of ROS mediated-ER stress. The in vivo results showed that shikonin effectively inhibited tumor growth in the HCT-116 and HCT-15 xenograft models. In conclusion, shikonin inhibited the proliferation of colorectal cancer cells in vitro and in vivo and warrants future investigation.

Keywords: Shikonin, Colorectal cancer, Endoplasmic reticulum stress, Apoptosis