In:
Chemotherapy, S. Karger AG, Vol. 50, No. 3 ( 2004), p. 119-126
Abstract:
〈 i 〉 Background: 〈 /i 〉 Phenolic compounds EGCG [(–)-epigallocatechin-3-gallate], resveratrol (3,4′,5-trihydroxy- 〈 i 〉 trans 〈 /i 〉 -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. 〈 i 〉 Methods: 〈 /i 〉 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. 〈 i 〉 Results: 〈 /i 〉 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. 〈 i 〉 Conclusions: 〈 /i 〉 These results suggest that HIF-1α-dependent gene expression participates in the cellular process of the hypoxia-induced resistance to phenolic compounds.
Type of Medium:
Online Resource
ISSN:
0009-3157
,
1421-9794
Language:
English
Publisher:
S. Karger AG
Publication Date:
2004
detail.hit.zdb_id:
1482111-4
SSG:
15,3
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