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KMID : 1140120120170020116
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Cancer Prevention Research
2012 Volume.17 No. 2 p.116 ~ p.120
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Curcumin Induces Apoptosis by the Regulation of AMPKα1 and HIF-1α Levels
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Abstract
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Under the hypoxic condition, cancer cells initiate their own adaptive pathways to have a facilitated oxygen and energy supply for survival. In this adaptive response, hypoxia-inducible factor-1α (HIF-1α) is a key regulator to stimulate angiogenesis, glucose transport and metabolism. We applied curcumin to examine the effect on HIF-1α induction and the regulatory effect of AMPKα1 on HIF-1α in HT-29 colon cancer cells. Our results showed that curcumin effectively induced apoptosis, dose dependently and reduced HIF-1α, which was elevated in hypoxic state induced by CoCl2. In addition, curcumin inhibited AMPKα1 activity, a modulator of adaptive pathway in response to hypoxia-induced energy depletion. These observations suggest that AMPKα1 may positively modulate HIF-1α stabilization and therefore, curcumin down-regulates AMPKα1 which seldom occurs in normoxic state. Curcumin induces apoptosis of HT-29 colon cancer cells through regulation of AMPKα1- HIF-1α pathway against hypoxic state.
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KEYWORD
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AMPK, Colon cancer, Curcumin, Hypoxia, HIF-1α
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