Antitumor and immunomodulatory activity of resveratrol on experimentally implanted tumor of H22 in Balb/c mice

Liu, Hongshan; Pan, Cheng-En; Yang, Wei; Liu, Xuemin

doi:10.3748/wjg.v9.i7.1474

Cited by 56 publications

(37 citation statements)

References 16 publications

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“…12 In our study, the delayed tumor development determined by Res was not associated with enhancement of immune responses. This finding agrees with previous data showing a lack of immunomodulatory effect after in vivo Res administration.…”

Section: 8-12supporting

confidence: 40%

“…In vivo supplementation with Res was shown to protect animals from transplanted parental tumors or from tumorigenesis induced by carcinogens. 1,[8][9][10][11][12] Although these data clearly demonstrated the cancer chemopreventive activity of Res, they may not be entirely relevant to the development of most cancers in humans, where the tumor arises spontaneously.…”

Section: Discussionmentioning

confidence: 90%

“…10 Res also inhibited the growth of experimentally implanted H22 tumors in mice through inhibition of cell cycle progression 11 or increased cytotoxicity of peritoneal macrophages. 12 Most data on the in vivo effect of Res have been drawn from studies performed in mice or rats transplanted with parental tumors or treated with carcinogens; while informative, these data may not be entirely relevant to the development of most cancers in humans, where the tumor is spontaneous and initiated by clonal expansion from a single cell in vivo.The HER-2/neu proto-oncogene encodes a receptor-like transmembrane protein with a relative m.w. of 185 kDa (p185) and homology to epidermal growth factor receptor.…”

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confidence: 99%

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Effect of resveratrol on the development of spontaneous mammary tumors in HER‐2/neu transgenic mice

Provinciali

Donnini

et al. 2005

Intl Journal of Cancer

113

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Resveratrol (Res) has been reported to possess cancer chemopreventive activity on the basis of its in vitro effects on tumor cells and in vivo experimental models of rodents transplanted with parental tumors or treated with carcinogens. We investigated the effects of Res on the development of mammary tumors appearing spontaneously in HER-2/neu transgenic mice at an early age. The mechanisms involved in the Res antitumor effect were evaluated by studying the immune effectiveness, tumor apoptosis and expression of mRNA and protein for HER-2/neu in tumoral mammary glands from Res-treated mice and in tumor cell lines. Res supplementation delayed the development of spontaneous mammary tumors (p < 0.001), reduced the mean number and size of mammary tumors (p < 0.0001) and diminished the number of lung metastases in HER-2/neu transgenic mice. The effects of Res were associated with downregulation of HER-2/neu gene expression and increased apoptosis both in tumoral mammary glands and in murine (N202) and human (SKBr3) tumor cell lines. Neither the basal, the IL-2-induced NK activity nor the lymphocyte number and proliferation was modified in Res-supplemented compared to control mice. Our results demonstrate that Res supplementation delays the development and reduces the metastasizing capacity of spontaneous mammary tumors in HER-2/neu transgenic mice. The antitumor effect of Res might be related to the downregulation of HER-2/neu expression and the induction of apoptosis in tumor cells. ' 2005 Wiley-Liss, Inc.Key words: resveratrol; HER-2/neu; mammary tumor; transgenic mouse; apoptosis Cancer chemoprevention, the prevention of cancer by chemical agents that reduce the risk of carcinogenesis, is one of the most direct ways to reduce morbidity and mortality. Res (trans-3,4 0 , 5-trihydroxystilbene) is a naturally occurring polyphenolic antioxidant compound present in grapes, mulberries, peanuts and red wine. It has been identified as an excellent candidate cancer chemopreventive, based on its safety and efficacy in experimental models of carcinogenesis. It has been found to inhibit diverse cellular events associated with tumor initiation, promotion and progression. 1 Most of the antitumor activity of Res has been discovered through in vitro studies in tumor cell lines. In these studies, Res was generally found to induce growth inhibition and apoptosis of a panel of human and murine tumor cell lines. [2][3][4][5][6][7] Fewer studies have been conducted on the antitumor effect exerted by in vivo supplementation with Res. Res was found to inhibit tumorigenesis in a mouse skin cancer model. 1 In other studies, it protected rats from ascites hepatoma 8 and colon carcinogenesis 9 and exerted inhibitory effects on tumor growth and lung metastasis in mice bearing highly metastatic Lewis lung carcinoma. 10 In the latter study, the effect of Res was related to its proapoptotic and antiangiogenic action on tumor cells, with no evidence of modulation of the immune response. 10 Res also inhibited the growth of experimentally implante...

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Section: 8-12supporting

confidence: 40%

Section: Discussionmentioning

confidence: 90%

mentioning

confidence: 99%

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Effect of resveratrol on the development of spontaneous mammary tumors in HER‐2/neu transgenic mice

Provinciali

Donnini

et al. 2005

Intl Journal of Cancer

113

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“…For example, diallyl disulfide (20) and resveratrol (21) have antitumorigenic activity in mouse xenograft models of tumorigenicity. Resveratrol is a phenolic compound, found in red wine and various fruits and vegetables, which has anticancer properties and modulated the expression of the antitumorigenic genes p53 and NSAID activated gene 1 (NAG-1; ref.…”

Section: Introductionmentioning

confidence: 99%

The anti-invasive activity of cyclooxygenase inhibitors is regulated by the transcription factor ATF3 (activating transcription factor 3)

Bottone

Moon

Kim

et al. 2005

Molecular Cancer Therapeutics

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We previously showed that nonsteroidal anti-inflammatory drugs (NSAID) such as sulindac sulfide, which has chemopreventive activity, modulate the expression of several genes detected by microarray analysis. Activating transcription factor 3 (ATF3) was selected for further study because it is a transcription factor involved in cell proliferation, apoptosis, and invasion, and its expression is repressed in human colorectal tumors as compared with normal adjacent tissue. In this report, we show that ATF3 mRNA and protein expression are up-regulated in HCT-116 human colorectal cancer cells following treatment with NSAIDs, troglitazone, diallyl disulfide, and resveratrol. To ascertain the biological significance of ATF3, we overexpressed full-length ATF3 protein in the sense and antisense orientations. Overexpression of ATF3 in the sense orientation decreased focus formation in vitro and reduced the size of mouse tumor xenografts by 54% in vivo. Conversely, overexpression of antisense ATF3 was protumorigenic in vitro, however, not in vivo. ATF3 in the sense orientation did not modulate apoptosis, indicating another mechanism is involved. With microarray analysis, several genes relating to invasion and metastasis were identified by ATF3 overexpression and were confirmed by real-time reverse transcription-PCR, and several of these genes were modulated by sulindac sulfide, which inhibited invasion in these cells. Furthermore, overexpression of ATF3 inhibited invasion to a similar degree as sulindac sulfide treatment, whereas antisense ATF3 increased invasion. In conclusion, ATF3 represents a novel mechanism in which NSAIDs exert their anti-invasive activity, thereby linking ATF3 and its gene regulatory activity to the biological activity of these compounds. [Mol Cancer Ther 2005;4(5):693 -703]

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“…Anticancer mechanisms of action for resveratrol, which have been described predominantly from in vitro studies, include the inhibition of transcription factors, kinases and other molecules involved in cell proliferation and survival. In animal models, resveratrol has demonstrated efficacy against breast, esophageal, lung and colon cancer, and was reported to decrease the extent of metastasis of melanoma and lung or colon carcinoma (29)(30)(31)(32)(33)(34)(35)(36)(37). However, resveratrol aglycone has been reported to protect certain types of cells from DNA damage.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol-3-O-glucuronide and resveratrol-4′-O-glucuronide reduce DNA strand breakage but not apoptosis in Jurkat T cells treated with camptothecin

Zunino

Storms

2017

Oncology Letters

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Abstract.Resveratrol has been reported to inhibit or induce DNA damage, depending upon the type of cell and the experimental conditions. Dietary resveratrol is present in the body predominantly as metabolites and limited data is available concerning the activities of these metabolic products. In the present study, physiologically obtainable levels of the resveratrol metabolites resveratrol-3-O-glucuronide, resveratrol-4'-O-glucuronide and resveratrol-3-O-sulfate were evaluated for their ability to protect Jurkat T cells against DNA damage induced by the topoisomerase I inhibitors camptothecin and topotecan. The cells were pretreated for 24 h with 10 µM resveratrol aglycone or each resveratrol metabolite prior to the induction of DNA damage with camptothecin or topotecan. In separate experiments, the cells were co-treated with resveratrol or its metabolites, and a topoisomerase I inhibitor. The detection of histone 2AX phosphorylation and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) were used to determine DNA damage, and apoptosis was measured using an antibody against cleaved poly ADP-ribose polymerase. It was identified that pretreatment of the cells with resveratrol-3-O-glucuronide and resveratrol-4'-O-glucuronide reduced the mean fluorescence intensity of staining for DNA strand breaks following treatment with camptothecin, while the percentage of cells undergoing apoptosis was unchanged. However, pretreatment of the cells with resveratrol aglycone increased the DNA damage and apoptosis induced by the drugs. These results suggest that the glucuronide metabolites of resveratrol partially protected the cells from DNA damage, but did not influence the induction of cell death by camptothecin and topotecan. These data suggest that resveratrol aglycone treatment may be beneficial for treating types of cancer that have direct contact with resveratrol prior to its metabolism, including gastrointestinal cancers, which are routinely treated with topoisomerase I inhibitors.

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Antitumor and immunomodulatory activity of resveratrol on experimentally implanted tumor of H22 in Balb/c mice

Abstract: Resveratrol could inhibit the growth of H22 tumor in Balb/c mice. The antitumor effect of resveratrol might be related to directly inhibiting the growth of H22 cells and indirectly inhibiting its potential effect on nonspecific host immunomodulatory activity.

Cited by 56 publications

References 16 publications

Effect of resveratrol on the development of spontaneous mammary tumors in HER‐2/neu transgenic mice

Effect of resveratrol on the development of spontaneous mammary tumors in HER‐2/neu transgenic mice

The anti-invasive activity of cyclooxygenase inhibitors is regulated by the transcription factor ATF3 (activating transcription factor 3)

Resveratrol-3-O-glucuronide and resveratrol-4′-O-glucuronide reduce DNA strand breakage but not apoptosis in Jurkat T cells treated with camptothecin

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