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Salternamide A Suppresses Hypoxia-Induced Accumulation of HIF-1α and Induces Apoptosis in Human Colorectal Cancer Cells

College of Pharmacy, Seoul National University, Seoul 151-742, Korea
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Academic Editor: Sylvia Urban
Mar. Drugs 2015, 13(11), 6962-6976; https://doi.org/10.3390/md13116962
Received: 28 August 2015 / Accepted: 12 November 2015 / Published: 19 November 2015
Hypoxia inducible factor-1α (HIF-1α) is an essential regulator of the cellular response to low oxygen concentrations, activating a broad range of genes that provide adaptive responses to oxygen deprivation. HIF-1α is overexpressed in various cancers and therefore represents a considerable chemotherapeutic target. Salternamide A (SA), a novel small molecule that is isolated from a halophilic Streptomyces sp., is a potent cytotoxic agent against a variety of human cancer cell lines. However, the mechanisms by which SA inhibits tumor growth remain to be elucidated. In the present study, we demonstrate that SA efficiently inhibits the hypoxia-induced accumulation of HIF-1α in a time- and concentration-dependent manner in various human cancer cells. In addition, SA suppresses the upstream signaling of HIF-1α, such as PI3K/Akt/mTOR, p42/p44 MAPK, and STAT3 signaling under hypoxic conditions. Furthermore, we found that SA induces cell death by stimulating G2/M cell cycle arrest and apoptosis in human colorectal cancer cells. Taken together, SA was identified as a novel small molecule HIF-1α inhibitor from marine natural products and is potentially a leading candidate in the development of anticancer agents. View Full-Text
Keywords: salternamide A (SA); HIF-1α; PI3K/Akt/mTOR; p42/p44 MAPK; STAT3; cell death salternamide A (SA); HIF-1α; PI3K/Akt/mTOR; p42/p44 MAPK; STAT3; cell death
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Bach, D.-H.; Kim, S.-H.; Hong, J.-Y.; Park, H.J.; Oh, D.-C.; Lee, S.K. Salternamide A Suppresses Hypoxia-Induced Accumulation of HIF-1α and Induces Apoptosis in Human Colorectal Cancer Cells. Mar. Drugs 2015, 13, 6962-6976.

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