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RSS FeedsMarine Drugs, Vol. 13, Pages 6962-6976: Salternamide A Suppresses Hypoxia-Induced Accumulation of HIF-1? and Induces Apoptosis in Human Colorectal Cancer Cells (Marine Drugs)

 
 

19 november 2015 15:16:56

 
Marine Drugs, Vol. 13, Pages 6962-6976: Salternamide A Suppresses Hypoxia-Induced Accumulation of HIF-1? and Induces Apoptosis in Human Colorectal Cancer Cells (Marine Drugs)
 


Hypoxia inducible factor-1? (HIF-1?) 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-1? 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-1? in a time- and concentration-dependent manner in various human cancer cells. In addition, SA suppresses the upstream signaling of HIF-1?, 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-1? inhibitor from marine natural products and is potentially a leading candidate in the development of anticancer agents.


 
302 viewsCategory: Biochemistry, Molecular Biology, Pharmacology
 
Marine Drugs, Vol. 13, Pages 6947-6961: A New Analogue of Echinomycin and a New Cyclic Dipeptide from a Marine-Derived Streptomyces sp. LS298 (Marine Drugs)
Marine Drugs, Vol. 13, Pages 7040-7054: Characterization of a Newly Isolated Marine Fungus Aspergillus dimorphicus for Optimized Production of the Anti-Tumor Agent Wentilactones (Marine Drugs)
 
 
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