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

Hui Qi; Xing Zhang; Huanhuan Liu; Meng Han; Xuzhen Tang; Shulan Qu; Xiaoyu Wang; Yifu Yang

doi:10.7150/jca.65297

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

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

Authors

Hui Qi^{1

2}, Xing Zhang¹, Huanhuan Liu², Meng Han², Xuzhen Tang², Shulan Qu¹, Xiaoyu Wang¹, Yifu Yang¹

Affiliations

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.

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: Apoptosis; Colorectal cancer; Endoplasmic reticulum stress; Shikonin.