期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 274, 期 -, 页码 58-67出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2017.06.029
关键词
Shikonin; HIF-1 alpha; Translation; mTOR; Antitumor activity
资金
- National Natural Science Foundation of China [81360496, 81660608, 81660344]
- Jilin Province Science and Technology Development Plan item [20150101229JC]
- Education Department of Jilin Province [2016.281]
Hypoxia enhances the development of solid tumors. Hypoxia-inducible factor-1 alpha(HIF-1 alpha) is a transcription factor that is dominantly expressed under hypoxia in solid tumor cells and is a key factor of tumor regulation. HIF-1 alpha regulates several target genes involved in many aspects of cancer progression, including angiogenesis, metastasis, and cell proliferation, as well as imparting resistance to cancer treatment. In this study, we assessed shikonin, which derives from the traditional medical herb Lithospermum erythrorhizon, for its anti-cancer effects in hypoxia-induced human colon cancer cell lines. Shikonin showed potent inhibitory activity against hypoxia-induced HIF-1 alpha activation in various human cancer cell lines and efficient scavenging activity of hypoxia-induced reactive oxygen species in tumor cells. Further analysis revealed that shikonin inhibited HIF-1 alpha protein synthesis without affecting the expression of HIF-1 alpha mRNA or degrading HIF-1 alpha protein. It was subsequently shown to attenuate the activation of downstream mTOR/p70S6K/4E-BP1/eIF4E kinase. Shikonin also dose-dependently caused the cell cycle arrest of activated HCT116 cells and inhibited the proliferation of HCT116 and SW620 cells. Moreover, it significantly inhibited tumor growth in a xenograft modal. These findings suggest that shikonin could be considered for use as a potential drug in human colon cancer therapy. (C) 2017 Elsevier B.V. All rights reserved.
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