Open AccessJournal Article
Suppression of 7,12-Dimethylbenz(a)anthracene-induced Mammary Carcinogenesis in Rats by Resveratrol Role of Nuclear Factor-κB, Cyclooxygenase 2, and Matrix Metalloprotease 9
TLDR
Results suggest that resveratrol suppresses DMBA-induced mammary carcinogenesis, which correlates with down-regulation of NF-kappaB, cyclooxygenase-2, and matrix metalloprotease-9 expression.Abstract:
We have reported recently that resveratrol ( trans -3,4′,5-trihydroxystilbene), a polyphenolic phytoalexin found in grapes, fruits, and root extracts of the weed Polygonum cuspidatum , is a potent inhibitor of nuclear factor (NF)-κB activation. Because NF-κB suppression has been linked with chemoprevention, this prompted us to investigate the chemopreventive potential of resveratrol by testing it against mammary carcinogenesis induced by 7,12-dimethylbenz( a )anthracene (DMBA) in female Sprague Dawley rats. Dietary administration of resveratrol (10 ppm) had no effect on body weight gain and tumor volume but produced striking reductions in the incidence (45%; P P in situ (7 of 7), whereas treatment with resveratrol suppressed DMBA-induced ductal carcinoma. Immunohistochemistry and Western blot analysis revealed that resveratrol suppressed the DMBA-induced cyclooxygenase-2 and matrix metalloprotease-9 expression in the breast tumor. Gel shift analysis showed suppression of DMBA-induced NF-κB activation by resveratrol. Treatment of human breast cancer MCF-7 cells with resveratrol also suppressed the NF-κB activation and inhibited proliferation at S-G 2 -M phase. Overall, our results suggest that resveratrol suppresses DMBA-induced mammary carcinogenesis, which correlates with down-regulation of NF-κB, cyclooxygenase-2, and matrix metalloprotease-9 expression.read more
Citations
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Cancer chemoprevention with dietary phytochemicals
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Molecular targets of dietary agents for prevention and therapy of cancer
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High absorption but very low bioavailability of oral resveratrol in humans
TL;DR: The dietary polyphenol resveratrol has been shown to have chemopreventive activity against cardiovascular disease and a variety of cancers in model systems, but it is not clear whether the drug reaches the proposed sites of action in vivo after oral ingestion, especially in humans.
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Nuclear factor-κB: The enemy within
TL;DR: The NF-kappaB proteins themselves and proteins regulated by it have been linked to cellular transformation, proliferation, apoptosis suppression, invasion, angiogenesis, and metastasis as mentioned in this paper.
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Role of Resveratrol in Prevention and Therapy of Cancer: Preclinical and Clinical Studies
Bharat B. Aggarwal,Anjana Bhardwaj,Rishi S. Aggarwal,Navindra P. Seeram,Shishir Shishodia,Yasunari Takada +5 more
TL;DR: In vivo, resveratrol blocks the multistep process of carcinogenesis at various stages: it blocks carcinogen activation by inhibiting aryl hydrocarbon-induced CYP1A1 expression and activity, and suppresses tumor initiation, promotion and progression.
References
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Journal ArticleDOI
Cell cycle effects and control of gene expression by resveratrol in human breast carcinoma cell lines with different metastatic potentials.
Tze-chen Hsieh,P Burfeind,K. Laud,Joseph M. Backer,Frank Traganos,Zbigniew Darzynkiewicz,Joseph M. Wu +6 more
TL;DR: The results suggest that the intrinsic metastatic potential of cancer cells may affect their responses to chemopreventive agents such as resveratrol.
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Estrogens, BRCA1, and breast cancer.
TL;DR: The role of premenopausal estrogens in breast cancer is discussed and more research is initiated to initiate more research that would lead to novel means of reducing breast cancer risk, particularly among BRCA1 mutation carriers.
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Resveratrol modulates arachidonic acid release, prostaglandin synthesis, and 3T6 fibroblast growth.
TL;DR: The results suggest that reactive oxygen species and AA, and/or prostag landins such as prostaglandin E(2) might be involved in the control of 3T6 fibroblast growth by resveratrol.
Journal ArticleDOI
Resveratrol inhibits cyclooxygenase-2 transcription in human mammary epithelial cells.
Kotha Subbaramaiah,Pedro Michaluart,Wen Jing Chung,Tadashi Tanabe,Nitin T. Telang,Andrew J. Dannenberg +5 more
TL;DR: Investigation of whether resveratrol, a chemopreventive agent found in grapes, could suppress phorbol ester‐mediated induction of COX‐2 in human mammary and oral epithelial cells found it to be inhibited.