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- Title
Hypoxia-Inducible Factor 1alpha-Mediated Resistance to Phenolic Anticancer.
- Authors
Ju-Yeon Hyun; Yang-Sook Chun; Tae-You Kim; Hye-Lim Kim; Myung-Suk Kim; Jong-Wan Park
- Abstract
Background: Phenolic compounds EGCG [(-)-epigallocatechin-3-gallate], resveratrol (3,4),5-trihydroxy-trans-stilbene) and capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) are worth investigating for clinical application in cancer prevention and chemotherapy. Hypoxia-induced drug resistance is a major obstacle in the development of effective cancer chemotherapy. Therefore, we examined whether drug resistance to these phenolic compounds is acquired by hypoxia. Methods: Hep3B hepatoma, Caki-1 renal carcinoma, SK-N-MC neuroblastoma, and HEK293 cell lines were cultured under normoxic or hypoxic conditions. Drug sensitivities to the phenolic compounds and expression of hypoxia-inducible factor-1α (HIF-1α) and the multidrug resistance genes were examined in these cell lines. Results: Drug resistance was acquired 24 h after hypoxia and subsided 8 h after reoxygenation. Protein synthesis inhibitors abolished this drug resistance. A transfection study demonstrated that HIF-1α enhanced this hypoxia-induced resistance and that its dominant-negative isoform suppressed resistance acquisition. However, MDR1 and MRP1, which provide multidrug resistance to conventional anticancer agents, were not induced by hypoxia. Conclusions: These results suggest that HIF-1α-dependent gene expression participates in the cellular process of the hypoxia-induced resistance to phenolic compounds.
- Subjects
PHENOLS; CAPSAICIN; DRUG resistance; HYPOXEMIA; CANCER chemoprevention; CANCER chemotherapy
- Publication
Chemotherapy (0009-3157), 2004, Vol 50, Issue 3, p119
- ISSN
0009-3157
- Publication type
Article
- DOI
10.1159/000077885