Conjugated linoleic acids inhibit hypoxia inducible factor-1α stabilization under hypoxic condition in human hepatocellular carcinoma cells.

Abstract

The anti-cancer effects of various fatty acids are drawing a lot of attention. To determine whether different fatty acids affect the hypoxic response of liver cancer cells, we examined the effects of various fatty acids on the stabilization of the hypoxia-inducible factor (HIF)-1α protein in the HepG2 human hepatocellular carcinoma (HCC) cell line under condition containing 1% O(2). Of the fatty acids examined, only 9cis, 11trans (c9, t11)-conjugated linoleic acid (CLA) and 10trans, 12cis (t10, c12)-CLA inhibited hypoxia-induced HIF-1α stabilization. In addition, HIF-1α prolyl hydroxylase or proteasome inhibition abrogated the effects of c9, t11- and t10, c12-CLA. Moreover, c9, t11- and t10, c12-CLA significantly inhibited cell proliferation and induced apoptotic cell death under hypoxia. This is the first study showing that c9, t11- and t10, c12-CLA inhibit the hypoxic response in HCC cells.

• Authors: Masao Yamasaki, Taku Nagatomo, Tetsuya Matsuyama, Yuri Ikeho, Emiko Kato, Kei Nishiyama, Yoichi Sakakibara, Masahito Suiko, Kazuo Nishiyama
• Journal: Journal of oleo science (J Oleo Sci) Vol. 61 Issue 9 Pg. 491-6 ( 2012) ISSN: 1347-3352 [Electronic] Japan
• PMID: 22975783 (Publication Type: Journal Article)

Chemical References

• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• Linoleic Acids, Conjugated

Topics

• Animals
• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (drug therapy, metabolism, pathology)
• Cell Cycle (drug effects)
• Dose-Response Relationship, Drug
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (antagonists & inhibitors, metabolism)
• Linoleic Acids, Conjugated (chemical synthesis, chemistry, pharmacology)
• Liver Neoplasms (drug therapy, metabolism, pathology)
• Protein Stability (drug effects)
• Structure-Activity Relationship
• Tumor Cells, Cultured