In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 458-458
Abstract:
Hypoxia-inducible factor-1α (HIF-1α), a transcription factor, over- expressed in many human tumors and their metastases, and is closely associated with more aggressive tumor phenotype. An important objective of anti-cancer therapy is the development of new drugs that suppress hypoxic responses in solid tumors. In many studies, resveratrol has been shown to chemopreventive effect in various cancer cells. However, resveratrol's biological activity is limited by its photosensitivity and metabolic instability. This study was investigated the effects of a novel analogue of resveratrol, HS-1793, on the expression levels of HIF-1α and vascular endothelial growth factor (VEGF) in PC-3 human prostate cancer cells. Hypoxic condition induced a time-dependent increase in the level of HIF-1α protein in PC-3 cells, and treatment with HS-1793 markedly decreased HIF-1α expression level. HS-1793 also inhibited VEGF expression level. Mechanistically, HS-1793 inhibited HIF-1α and VEGF expression through multiple mechanisms. Firstly, HS-1793 inhibited both PI3K and Erk phosphorylations in PC-3 cells. Secondly, HS-1793 substantially induced HIF-1α protein degradation through the proteasome pathway. Finally, HS-1793 inhibited hypoxia-induced cell migration. These data suggested that HS-1793 may inhibit human prostate cancer progression and angiogenesis by inhibiting HIF-1α and VEGF expression. Moreover, HS-1793 showed more potent effect than resveratrol on the cytotoxic effects on PC-3 cells. Taken together, these results implied that HS-1793, a novel analogue of resveratrol, might be a new potent chemopreventive agent against human prostate cancer cells. [This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (R01-2006-000-11117-0)]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 458.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM10-458
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2010
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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