A novel resveratrol analogue, HS-1793, inhibits hypoxia-induced HIF-1α and VEGF expression, and migration in human prostate cancer cells

Kim, Dong Hwan; Hossain, Mohammad Akbar; Kim, Min Young; Kim, Jinah; Yoon, Ju-Duk; Suh, Hyo-Weon; Kim, Gi‐Young; Choi, Yung Hyun; Chung, Hae Young; Kim, Nam Deuk

doi:10.3892/ijo.2013.2116

Cited by 25 publications

(19 citation statements)

References 31 publications

(30 reference statements)

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“…Accumulating evidence indicates that hypoxic conditions activate several signaling pathways, including PI3K/AKT, glycogen synthase kinase 3 beta (GSK-3β), and ERK (4,5). In this study, hypoxic conditions induced PI3K/AKT and ERK in HCT116 cells (Fig.…”

Section: Discussionmentioning

confidence: 78%

“…Under normoxic conditions, HIF-1α protein is efficiently degraded by the ubiquitin protein ligase Von Hippel-Lindeau (VHL) and thus does not exert its effects (3). Several compounds have been tested as inhibitors of hypoxia-induced HIF-1α expression in cancer cells (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

“…Cell survival was quantified by an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrasolium bromide; Sigma-Aldrich) assay to measure mitochondrial activity in viable cells. Cells seeded at a density of 1x10 5 per well were allowed to adhere overnight, after which the culture media were replaced with fresh media. Cells were exposed to sulforaphane at concentrations of 12.5, 25 and 50 µM for 6 h under normoxic and hypoxic conditions.…”

Section: Introductionmentioning

confidence: 99%

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Sulforaphane inhibits hypoxia-induced HIF-1α and VEGF expression and migration of human colon cancer cells

Kim

Sung

Kang

et al. 2015

International Journal of Oncology

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Abstract. The effects of sulforaphane (a natural product commonly found in broccoli) was investigated on hypoxia inducible factor-1α (HIF-1α) expression in HCT116 human colon cancer cells and AGS human gastric cancer cells. We found that hypoxia-induced HIF-1α protein expression in HCT116 and AGS cells, while treatment with sulforaphane markedly and concentration-dependently inhibited HIF-1α expression in both cell lines. Treatment with sulforaphane inhibited hypoxia-induced vascular endothelial growth factor (VEGF) expression in HCT116 cells. Treatment with sulforaphane modulated the effect of hypoxia on HIF-1α stability. However, degradation of HIF-1α by sulforaphane was not mediated through the 26S proteasome pathway. We also found that the inhibition of HIF-1α by sulforaphane was not mediated through AKT and extracellular signal-regulated kinase phosphorylation under hypoxic conditions. Finally, hypoxiainduced HCT116 cell migration was inhibited by sulforaphane. These data suggest that sulforaphane may inhibit human colon cancer progression and cancer cell angiogenesis by inhibiting HIF-1α and VEGF expression. Taken together, these results indicate that sulforaphane is a new and potent chemopreventive drug candidate for treating patients with human colon cancer. IntroductionHypoxic conditions are associated with increased tumor growth and metastasis, as well as poor survival in cancer patients (1). Hypoxia inducible factor-1α (HIF-1α) is a key protein that is expressed under hypoxic conditions and promotes vascular remodeling by vascular endothelial growth factor (VEGF). VEGF is one of the most critical factors that stimulate angiogenesis. Therefore, inhibition of HIF -1α and VEGF has demonstrated therapeutic efficacy in the treatment of several types of cancer. Expression of VEGF is regulated by hypoxia, growth factors, and oncogenes (2). HIF-1 is a heterodimeric transcription factor composed of HIF-1α and aryl hydrocarbon receptor nuclear translocator (ARNT, HIF-1β), which translocates to the nucleus and binds to hypoxia response element (HRE) binding sites. Under normoxic conditions, HIF-1α protein is efficiently degraded by the ubiquitin protein ligase Von Hippel-Lindeau (VHL) and thus does not exert its effects (3). Several compounds have been tested as inhibitors of hypoxia-induced HIF-1α expression in cancer cells (4-6).Various natural products and their analogues are currently being researched as chemopreventive agents (7-9). Sulforaphane is a potent isothiocyanate derivative found in broccoli and other vegetables, such as Brussels sprouts and cabbage, and has various health benefits, including anticancer and antioxidant properties (8,10). Many studies have revealed that sulforaphane activates phase 2 antioxidant enzymes via nuclear factor E2-related factor 2 (Nrf2) (11)(12)(13)(14). In the last decade, many studies revealed that sulforaphane acts as a chemopreventive agent by inducing apoptosis and cell cycle arrest and inhibiting proliferation. In colon cancer cells, sulforaphane induced apoptosis ...

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Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sulforaphane inhibits hypoxia-induced HIF-1α and VEGF expression and migration of human colon cancer cells

Kim

Sung

Kang

et al. 2015

International Journal of Oncology

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“…Furthermore, chronic studies are an absolute must, as it is still unclear if RSV supplementation on the longer term is beneficial for overall health status [111]. A synthetic analogue of RSV, HS-1793, may be a new potent chemopreventive agent against human prostate and breast cancer cells [121, 122]. HS-1793 showed more potent anticancer effects in several aspects compared to RSV in MCF-7 (wild-type p53) and MDA-MB-231 (mutant p53) cells [122].…”

Section: Antioxidant Supplementation In Humans: Does It Make Sense?mentioning

confidence: 99%

Effect of Antioxidants Supplementation on Aging and Longevity

Sadowska-Bartosz

Bartosz

2014

BioMed Research International

222

143

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If aging is due to or contributed by free radical reactions, as postulated by the free radical theory of aging, lifespan of organisms should be extended by administration of exogenous antioxidants. This paper reviews data on model organisms concerning the effects of exogenous antioxidants (antioxidant vitamins, lipoic acid, coenzyme Q, melatonin, resveratrol, curcumin, other polyphenols, and synthetic antioxidants including antioxidant nanoparticles) on the lifespan of model organisms. Mechanisms of effects of antioxidants, often due to indirect antioxidant action or to action not related to the antioxidant properties of the compounds administered, are discussed. The legitimacy of antioxidant supplementation in human is considered.

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“…It has been widely researched for its antioxidant properties, most specifically in cancer and cardiovascular diseases [6][7][8][9]. In some human studies, resveratrol can decrease signs of inflammation with virtually no side effects [8,10].…”

Section: Introductionmentioning

confidence: 99%