Shikonin induces apoptosis and prosurvival autophagy in human melanoma A375 cells via ROS-mediated ER stress and p38 pathways

Artificial Cells, Nanomedicine, and Biotechnology

Zhexing Shou¹  Yuwei Bai²  Yongkang Liu²  Geng Niu²  Xing Kang²  Bin Li²  Senlin He²  Houyan Hao²  Tingting Zhang²  Yi Li³  Chao Chen⁴ 

[1] Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Ministry of Education, Key Laboratory of Resource Biology and Biotechnology in Western China, Northwest University, Xi'an, China;School of Computer Science, Xi’an Polytechnic University, Xi’an, China;School of Life Sciences, Northwest University, Xi'an, Shaanxi, China;

关键词: Shikonin;    apoptosis;    autophagy;    ROS;    ER stress;    p38;   

DOI  :  10.1080/21691401.2019.1575229

来源: DOAJ

【 摘 要 】

Shikonin, a botanical drug extracted from Lithospermum erythrorhizon, exhibits anti-cancer effects in various cancer cell lines. However, the mechanisms underlying these effects have not been completely elucidated yet. Here, we showed that Shikonin induces apoptosis and autophagy in A375 cells and inhibits their proliferation. Shikonin caused G2/M phase arrest through upregulation of p21 and downregulation of cyclin B1. Shikonin significantly triggered ER stress-mediated apoptosis by upregulating the expression of p-eIF2α, CHOP, and cleaved caspase-3. It also induced protective autophagy by activating the p38 pathway, followed by an increase in the levels of p-p38, LC3B-II, and Beclin 1. Upon suppression of autophagy by 3-methyladenine, Shikonin-induced apoptosis was enhanced in A375 cells. Moreover, after pretreatment with N-acetyl-cysteine, Shikonin increased the production of reactive oxygen species that are involved in regulating ER stress-mediated apoptosis and p38-activated autophagy, as evidenced by the reversion of cell viability and apoptosis and a decrease in p-eIF2α, CHOP, p-p38, LC3B-II, and Beclin 1 levels. Thus, we demonstrated that Shikonin induced apoptosis and autophagy in A375 cells via the activation of ROS-mediated ER stress and p38 pathways, indicating that Shikonin can serve as a potential agent for human melanoma therapy.

【 授权许可】

Unknown