Cancer Chemopreventive Activity of Resveratrol, a Natural Product Derived from Grapes

Jang, Meishiang; Cai, Lining; Udeani, George; Slowing, Karla; Thomas, Cathy F.; Beecher, Christopher W.W.; Fong, Harry H. S.; Farnsworth, Norman R.; Kinghorn, A. Douglas; Mehta, Rajendra G.; Moon, Richard C.; Pezzuto, John M.

doi:10.1126/science.275.5297.218

Cited by 4,459 publications

(2,916 citation statements)

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“…Similar findings have been reported in human mammary epithelial cells, in which resveratrol inhibited phorbol myristate acetate (PMA)-induced PGE 2 production by blocking transcription and COX enzyme function (32). Studies investigating resveratrol-mediated inhibition of COX in other cell types have demonstrated inhibition of peroxidase function, with no effect on COX enzyme activity (33,34).…”

Section: Discussionsupporting

confidence: 68%

The antioxidant resveratrol protects against chondrocyte apoptosis via effects on mitochondrial polarization and ATP production

Dave

Attur

Palmer

et al. 2008

Arthritis & Rheumatism

122

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Objective. To determine the effects of the antioxidant resveratrol on the functions of human chondrocytes in osteoarthritis (OA).Methods. Chondrocytes and cartilage explants were isolated from OA patients undergoing knee replacement surgery. Effects of resveratrol in the presence or absence of interleukin-1␤ (IL-1␤) stimulation were assessed by measurement of prostaglandin E 2 (PGE 2 ) and leukotriene B 4 (LTB 4 ) synthesis, cyclooxygenase (COX) activity, matrix metalloproteinase (MMP) expression, and proteoglycan production. To explore the mechanisms of action of resveratrol, its effects on mitochondrial function and apoptosis were examined by assessing mitochondrial membrane potential, ATP levels, cytochrome c release, and annexin V staining.Results. Resveratrol inhibited both spontaneous and IL-1␤-induced PGE 2 production by >20% (P < 0.05) and by 80% (P < 0.001), respectively; similarly, LTB 4 production was reduced by >50% (P < 0.05). The production of PGE 2 was inhibited via a 70-90% suppression of COX-2 expression and enzyme activity (P < 0.05). Resveratrol also promoted anabolic effects in OA explant cultures, by elevating proteoglycan synthesis and decreasing production of MMPs 1, 3, and 13. Pretreatment of OA chondrocytes with resveratrol blocked mitochondrial membrane depolarization, loss of mitochondrial biomass, and IL-1␤-induced ATP depletion. Similarly, IL-1␤-mediated induction of the apoptotic markers cytochrome c and annexin V was also inhibited by resveratrol. Exogenous addition of PGE 2 abolished the protective effects of resveratrol on mitochondrial membrane integrity, ATP levels, expression of apoptotic markers, and DNA fragmentation.Conclusion. Resveratrol protects against IL-1␤-induced catabolic effects and prevents chondrocyte apoptosis via its inhibition of mitochondrial membrane depolarization and ATP depletion. These beneficial effects of resveratrol are due, in part, to its capacity to inhibit COX-2-derived PGE 2 synthesis. Resveratrol may therefore protect against oxidant injury and apoptosis, which are main features of progressive OA.

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Section: Discussionsupporting

confidence: 68%

The antioxidant resveratrol protects against chondrocyte apoptosis via effects on mitochondrial polarization and ATP production

Dave

Attur

Palmer

et al. 2008

Arthritis & Rheumatism

122

View full text Add to dashboard Cite

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“…Furthermore, they can protect cells from oxidative damage and programmed cell death [7] . Antioxidants prevent carcinogenesis in murine model with anti-apoptotic activity [8] .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of anti–apoptotic activity of different dietary antioxidants in renal cell carcinoma against hydrogen peroxide

Rai

Mangal

Sahu

et al. 2011

Asian Pacific Journal of Tropical Biomedicine

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“…Other SERMs like idoxifene (Idox) (Chander et al, 1991;Nuttall et al, 1998), GW 5638 (Willson et al, 1994(Willson et al, , 1997Connor et al, 2001) and EM 800 (Luo et al, 1998;Labrie et al, 1999;Martel et al, 2000) are different from tamoxifen and based on their activity in the rodent uterus are more closely related to raloxifene. Resveratrol (Res) does not formally belong to the SERM family, because it is a phytoestrogen found in the plants (Jang et al, 1997), however Res has similar in vivo characteristics to the SERMs (Mizutani et al, 2000;Bhat and Pezzuto, 2001;Wu et al, 2001). ICI 182,780 (ICI) is a pure anti-oestrogen with anti-oestrogenic activities in almost all tissues, with no changes in serum lipids and on bone density (Wakeling and Bowler, 1987;Wakeling et al, 1991;Lee et al, 2000).…”

mentioning

confidence: 99%

Molecular classification of selective oestrogen receptor modulators on the basis of gene expression profiles of breast cancer cells expressing oestrogen receptor α

Levenson¹,

Kliakhandler²,

Svoboda³

et al. 2002

Br J Cancer

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The purpose of this study was to classify selective oestrogen receptor modulators based on gene expression profiles produced in breast cancer cells expressing either wtERa or mutant 351 ERa. In total, 54 microarray experiments were carried out by using a commercially available Atlas cDNA Expression Arrays (Clontech), containing 588 cancer-related genes. Nine sets of data were generated for each cell line following 24 h of treatment: expression data were obtained for cells treated with vehicle EtOH (Control); with 10 79 or 10 78 M oestradiol; with 10 76 M 4-hydroxytamoxifen; with 10 76 M raloxifene; with 10 76 M idoxifene, with 10 76 M EM 652, with 10 76 M GW 7604; with 5610 75 M resveratrol and with 10 76 M ICI 182,780. We developed a new algorithm 'Expression Signatures' to classify compounds on the basis of differential gene expression profiles. We created dendrograms for each cell line, in which branches represent relationships between compounds. Additionally, clustering analysis was performed using different subsets of genes to assess the robustness of the analysis. In general, only small differences between gene expression profiles treated with compounds were observed with correlation coefficients ranged from 0.83 to 0.98. This observation may be explained by the use of the same cell context for treatments with compounds that essentially belong to the same class of drugs with oestrogen receptors related mechanisms. The most surprising observation was that ICI 182,780 clustered together with oestrodiol and raloxifene for cells expressing wtERa and clustered together with EM 652 for cells expressing mutant 351 ERa. These data provide a rationale for a more precise and elaborate study in which custom made oligonucleotide arrays can be used with comprehensive sets of genes known to have consensus and putative oestrogen response elements in their promoter regions.

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Cancer Chemopreventive Activity of Resveratrol, a Natural Product Derived from Grapes

Cited by 4,459 publications

References 23 publications

The antioxidant resveratrol protects against chondrocyte apoptosis via effects on mitochondrial polarization and ATP production

The antioxidant resveratrol protects against chondrocyte apoptosis via effects on mitochondrial polarization and ATP production

Evaluation of anti–apoptotic activity of different dietary antioxidants in renal cell carcinoma against hydrogen peroxide

Molecular classification of selective oestrogen receptor modulators on the basis of gene expression profiles of breast cancer cells expressing oestrogen receptor α

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