Journal
PHYTOCHEMISTRY LETTERS
Volume 4, Issue 2, Pages 75-78Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.phytol.2010.09.003
Keywords
Thyrsiferol; Hypoxia-inducible factor-1 (HIF-1); Laurencia; Triterpene polyether; Marine natural product; Mitochondrial complex I inhibitor; NADH-ubiquinone oxidoreductase
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Funding
- NIH [CA98787]
- NOAA/NIUST [NA16RU1496]
- NIH Research Facilities [C06 RR-14503-01]
- CAPES
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The cytotoxic marine red algal metabolite thyrsiferol (1) was found to inhibit hypoxia-induced hypoxia-inducible factor-1 (HIF-1) activation in T47D human breast tumor cells (66% inhibition at 3 mu M). Compound 1 also suppressed hypoxic induction of HIF-1 target genes (VEGF, GLUT-1) at the mRNA level, and displayed tumor cell line-selective time-dependent inhibition of cell viability/proliferation. Mechanistic studies revealed that 1 selectively suppressed mitochondrial respiration at complex I (IC(50) 3 mu M). Thyrsiferol represents a prototypical, structurally unique electron transport chain inhibitor. The apparent rotenone-like activity may contribute to the observed cytotoxicity of 1 and play an important role in Laurencia chemical defense. (C) 2010 Phytochemical Society of Europe. Published by Elsevier B. V. All rights reserved.
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