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

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

Publication date: Dec 01, 2019

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-eIF2?, 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-eIF2?, 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.

Liu, Y., Kang, X., Niu, G., He, S., Zhang, T., Bai, Y., Li, Y., Hao, H., Chen, C., Shou, Z., and Li, B. Shikonin induces apoptosis and prosurvival autophagy in human melanoma A375 cells via ROS-mediated ER stress and p38 pathways. 24980. 2019 Artif Cells Nanomed Biotechnol (47):1.

Concepts Keywords
Acetyl Melanoma therapy
Apoptosis Anti cancer
Autophagy Potential agent melanoma
Cancer Branches of biology
Caspase 3 Cell biology
CHOP Programmed cell death
Cyclin Immunology
Cysteine Protein kinases
Downregulation Cellular processes
EIF2 Autophagy
M Phase Cellular senescence
Melanoma Reactive oxygen species
Oxygen P38
P21 Apoptosis
P38 Apoptosis
ROS
Stress

Semantics

Type Source Name
pathway KEGG Apoptosis
pathway KEGG Autophagy
disease MESH melanoma
pathway KEGG Melanoma
disease MESH cancer
drug DRUGBANK 3-Methyladenine
drug DRUGBANK L-Cysteine
pathway KEGG Cell cycle
disease MESH Endoplasmic Reticulum Stress

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