Resveratrol inhibits hypoxia-induced accumulation of hypoxia-inducible factor-1α and VEGF expression in human tongue squamous cell carcinoma and hepatoma cells

Zhang, Qunzhou; Tang, Xudong; Lu, Qing-Yi; Zhang, Zuo‐Feng; Brown, Jimmy J.; Le, Anh D.

doi:10.1158/1535-7163.mct-05-0198

Cited by 177 publications

(117 citation statements)

References 47 publications

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“…In the present study, IGF-I did not obviously up-regulate HIF-1α mRNA levels in MCF-7 cells ( Figure 2C). Previous studies (ours and others') have demonstrated that several natural products have no effect on HIF-1α mRNA levels, although they can inhibit HIF-1α protein accumulation [8,29,30] . Similarly, we also found that Dau at any concentration did not significantly affect HIF-1α mRNA expression in response to IGF-I ( Figure 2C), suggesting that Dau inhibited IGF-I-induced HIF-1α protein accumulation via some post-transcriptional mechanism(s).…”

Section: Discussionmentioning

confidence: 62%

Dauricine inhibits insulin-like growth factor-I-induced hypoxia inducible factor 1α protein accumulation and vascular endothelial growth factor expression in human breast cancer cells

Tang

Zhou

2009

Acta Pharmacol Sin

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Section: Discussionmentioning

confidence: 62%

Dauricine inhibits insulin-like growth factor-I-induced hypoxia inducible factor 1α protein accumulation and vascular endothelial growth factor expression in human breast cancer cells

Tang

Zhou

2009

Acta Pharmacol Sin

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“…Lin reported that RSV protects against oxidized LDL-induced breakage of the blood-brain barrier . Limited evidence showed that RSV regulates VEGF level in vascular ECs; however, decreased VEGF level caused by RSV treatment was observed in gingival fibroblasts (Nunez et al 2010), retinal cells (Dugas et al 2010), tongue squamous cell carcinoma, and hepatoma cells (Zhang et al 2005). Based on these data, we hypothesized that RSV may regulate high-glucoseinduced hyperpermeability via VEGF pathway.…”

Section: Introductionmentioning

confidence: 83%

Resveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae via VEGF/KDR pathway

Tian

Zhang

et al. 2012

Genes Nutr

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Endothelial hyperpermeability induced by hyperglycemia is the initial step in the development of atherosclerosis, one of the most serious cardiovascular complications in diabetes. In the present study, we investigated the effects of resveratrol (RSV), a bioactive ingredient extracted from Chinese herb rhizoma polygonum cuspidatum, on permeability in vitro and the molecular mechanisms involved. Permeability was assessed by the efflux of fluorescein isothiocyanate (FITC)-dextran permeated through the monolayer endothelial cells (ECs). The mRNA levels, protein expressions, and secretions were measured by quantitative real-time PCR, western blot, and ELISA, respectively. Increased permeability and caveolin-1 (cav-1) expression were observed in monolayer ECs exposed to high glucose. Resveratrol treatment alleviated the hyperpermeability and the overexpression of cav-1 induced by high glucose in a dose-dependent manner. b-Cyclodextrin, a structural inhibitor of caveolae, reduced the hyperpermeability caused by high glucose. Resveratrol also down-regulated the increased expressions of vascular endothelial growth factor (VEGF) and kinase insert domain receptor (KDR, or VEGF receptor-2) induced by high glucose. Inhibition of VEGF/KDR pathway by using SU5416, a selective inhibitor of KDR, alleviated the hyperpermeability and the cav-1 overexpression induced by high glucose. The above results demonstrate that RSV ameliorates caveolae-mediated hyperpermeability induced by high glucose via VEGF/KDR pathway.

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“…Although the involvement of mitogenactivated protein kinase (MAPK) pathway in maintaining the stability of HIF-1a has been contradictory in literature (Richard et al, 1999;Hur et al, 2001), we and others have shown that inhibition of p42/p44 ERKs by PD98059 diminished the stability of HIF-1a (Yoo et al, 2003(Yoo et al, , 2004Li et al, 2004;Zhang et al, 2005). Consistent with the previous results, activation of p42/p44 ERKs as well as stability of HIF-1a was significantly induced under hypoxia and repressed by PD98059 ( Figure 3d) (Yoo et al, 2003(Yoo et al, , 2004Li et al, 2004;Zhang et al, 2005). Similarly, 6-MP increased phosphorylated p42/p44 ERKs, whereas PD98059 decreased the phosphorylation of p42/p44 as well as the protein level of both HIF-1a and Nur77 ( Figure 3d).…”

Section: -Mp Enhances Transcriptional Activity Of Hif-1a Y-g Yoo Et Almentioning

confidence: 98%

6-Mercaptopurine, an activator of Nur77, enhances transcriptional activity of HIF-1α resulting in new vessel formation

et al. 2006

Oncogene

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Hypoxia-inducible factor-1a (HIF-1a) plays a central role in oxygen homeostasis. Previously, we reported that the orphan nuclear receptor Nur77 functions in stabilizing HIF-1a. Here, we demonstrate that 6-mercaptopurine (6-MP), an activator of the NR4A family members, enhances transcriptional activity of HIF-1. 6-MP enhanced the protein-level of HIF-1a as well as vascular endothelial growth factor (VEGF) in a dose-and timedependent manner. The induction of HIF-1a was abolished by the transfection of either a dominant-negative Nur77 mutant or si-Nur77, indicating a critical role of Nur77 in the 6-MP action. The HIF-1a protein level remained up to 60 min in the presence of 6-MP when de novo protein synthesis was blocked by cycloheximide, suggesting that 6-MP induces stabilization of the HIF-1a protein. The fact that 6-MP decreased the association of HIF-1a with von Hippel-Lindau protein and the acetylation of HIF-1a, may explain how 6-MP induced stability of HIF-1a. Further, 6-MP induced the transactivation function of HIF-1a by recruiting co-activator cyclic-AMP-responseelement-binding protein. Finally, 6-MP enhanced the expression of HIF-1a and VEGF, and the formation of capillary tubes in human umbilical vascular endothelial cells. Together, our results provide a new insight for 6-MP action in the stabilization of HIF-1a and imply a potential application of 6-MP in hypoxia-associated human vascular diseases.

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Resveratrol inhibits hypoxia-induced accumulation of hypoxia-inducible factor-1α and VEGF expression in human tongue squamous cell carcinoma and hepatoma cells

Cited by 177 publications

References 47 publications

Dauricine inhibits insulin-like growth factor-I-induced hypoxia inducible factor 1α protein accumulation and vascular endothelial growth factor expression in human breast cancer cells

Dauricine inhibits insulin-like growth factor-I-induced hypoxia inducible factor 1α protein accumulation and vascular endothelial growth factor expression in human breast cancer cells

Resveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae via VEGF/KDR pathway

6-Mercaptopurine, an activator of Nur77, enhances transcriptional activity of HIF-1α resulting in new vessel formation

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