Resveratrol and its analogues: promising antitumor agents.
31 May 2011-Anti-cancer Agents in Medicinal Chemistry (Anticancer Agents Med Chem)-Vol. 11, Iss: 5, pp 479-490
TL;DR: Resveratrol has been identified as an effective candidate for cancer chemoprevention based on its striking inhibitory effects on cellular events associated with cancer initiation, promotion, and progression.
Abstract: Resveratrol, a well-known natural product and a major component in grape, has attracted considerable attention as one of the most promising cancer during the past decade. Many studies have established that resveratrol can exert a broad range of biological activities including ceramide-mediated proapoptotic, antineoplastic, apoptosis-inducing, etc. Most important, resveratrol has been identified as an effective candidate for cancer chemoprevention based on its striking inhibitory effects on cellular events associated with cancer initiation, promotion, and progression. This review describes the general properties of resveratrol and its potential effect against cancer including its evidences as an antitumor agent in vitro, in vivo and clinically. In addition, we also summarized the structure-activity relationship of resveratrol and its analogues regarding the antitumor effects.
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TL;DR: Potential natural cancer preventive compounds, their molecular targets, and their mechanisms of actions are discussed.
Abstract: Cancer is the second leading cause of death worldwide. There is greater need for more effective and less toxic therapeutic and preventive strategies. Natural products are becoming an important research area for novel and bioactive molecules for drug discovery. Phytochemicals and dietary compounds have been used for the treatment of cancer throughout history due to their safety, low toxicity, and general availability. Many active phytochemicals are in human clinical trials. Studies have indicated that daily consumption of dietary phytochemicals have cancer protective effects against carcinogens. They can inhibit, delay, or reverse carcinogenesis by inducing detoxifying and antioxidant enzymes systems, regulating inflammatory and proliferative signaling pathways, and inducing cell cycle arrest and apoptosis. Epidemiological studies have also revealed that high dietary intakes of fruits and vegetables reduce the risk of cancer. This review discusses potential natural cancer preventive compounds, their molecular targets, and their mechanisms of actions.
144 citations
TL;DR: It is postulate that the disproportional up-regulation of SOD, CAT and GPX expression and enzymatic activity in cancer cells results in the mitochondrial accumulation of H2O2, which in turn induces cancer cell apoptosis.
Abstract: Resveratrol (RSV) is a natural polyphenol that is known as a powerful chemopreventive and chemotherapeutic anticancer molecule. This study focused on the effects of RSV on the activities and expression levels of antioxidant enzymes in the cancer cells. Prostate cancer PC-3 cells, hepatic cancer HepG2 cells, breast cancer MCF-7 cells and the non-cancerous HEK293T kidney epithelial cells were treated with a wide range of RSV concentrations (10-100 μM) for 24-72 h. Cell growth was estimated by trypan blue staining, activities of the antioxidant enzymes were measured spectrophotometrically, expression levels of the antioxidant enzymes were quantified by digitalizing the protein band intensities on Western blots, and the percentage of apoptotic cells was determined by flow cytometry. Treatment with a low concentration of RSV (25 μM) significantly increased superoxide dismutase (SOD) activity in PC-3, HepG2 and MCF-7 cells, but not in HEK293T cells. Catalase (CAT) activity was increased in HepG2 cells, but no effect was found on glutathione peroxidase (GPX) upon RSV treatment. RSV-induced SOD2 expression was observed in cancer cells, although the expression of SOD1, CAT and GPX1 was unaffected. Apoptosis increased upon RSV treatment of cancer cells, especially in PC-3 and HepG2 cells. Together, our data demonstrated that RSV inhibits cancer cell growth with minimal effects on non-cancerous cells. We postulate that the disproportional up-regulation of SOD, CAT and GPX expression and enzymatic activity in cancer cells results in the mitochondrial accumulation of H2O2, which in turn induces cancer cell apoptosis.
107 citations
Cites background from "Resveratrol and its analogues: prom..."
...RSV has been considered as an effective chemo-preventive agent against different cancers by hindering cancer initiation, promotion, and progression (Huang and Zhu, 2011; Jang et al., 1997)....
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TL;DR: Natural products have been used for the treatment of various diseases and are becoming an important research area for drug discovery, especially phytochemicals, which have exhibited anti-carcinogenic activities.
Abstract: Natural products have been used for the treatment of various diseases and are becoming an important research area for drug discovery. These products, especially phytochemicals have been extensively studies and have exhibited anti-carcinogenic activities by interfering with the initiation, development and progression of cancer through the modulation of various mechanisms including cellular proliferation, differentiation, apoptosis, angiogenesis, and metastasis. This concept is gaining attention because it is a cost-effective alternative to cancer treatment. In this article, we have discussed some of the naturally occurring products used in cancer treatment.
98 citations
Cites background from "Resveratrol and its analogues: prom..."
...[13] Resveratrol has been identified as an effective candidate for cancer prevention based on inhibitory effects on cellular events associated with cancer initiation, promotion, and progression.[14] It has been shown to inhibit tumor necrosis factor‐α‐mediated matrix metalloproteinase‐9 expression in HepG2 cells by down regulation of the nuclear factor‐kB signaling pathway....
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TL;DR: This review focuses on the structure–activity relationship of the key compounds containing a stilbene scaffold and describes how the structural modifications affect their anticancer activity.
Abstract: Stilbene is an abundant structural scaffold in nature, and stilbene-based compounds have been widely reported for their biological activity. Notably, (E)-resveratrol and its natural stilbene-containing derivatives have been extensively investigated as cardioprotective, potent antioxidant, anti-inflammatory, and anticancer agents. Starting from its potent chemotherapeutic activity against a wide variety of cancers, the stilbene scaffold has been subject to synthetic manipulations with the aim of obtaining new analogues with improved anticancer activity and better bioavailability. Within the last decade, the majority of new synthetic stilbene derivatives have demonstrated significant anticancer activity against a large number of cancer cell lines, depending on the type and position of substituents on the stilbene skeleton. This review focuses on the structure-activity relationship of the key compounds containing a stilbene scaffold and describes how the structural modifications affect their anticancer activity.
90 citations
TL;DR: Results indicate that resveratrol inhibits the migration of MDA231 cells by reversing TGF-β1-induced EMT and inhibits the lung metastasis of Mda231 human breast cancer in a xenograft-bearing mouse model.
Abstract: Metastasis is a major cause of death in patients with breast cancer. In the process of cancer development, epithelial-mesenchymal transition (EMT) is crucial to promoting the invasion and migration of tumor cells. In a previous study, the role of resveratrol in migration and metastasis was investigated in MDA-MB-231 (MDA231) human breast cancer cells and a xenograft-bearing mouse model. Additionally, the related mechanism was explored. In the present study, in vitro Transwell assays showed that resveratrol can inhibit the migration of transforming growth factor (TGF)-β1-induced MDA231 cells in a concentration-dependent manner. An enzyme-linked immunosorbent assay (ELISA) showed that resveratrol can reduce the secretion of matrix metalloproteinase (MMP)-2 and MMP-9. Immunofluorescence was performed to confirm the expression of EMT-related markers. Immunofluorescence assays confirmed that resveratrol changed the expression of the EMT-related markers E-cadherin and vimentin. Western blot analysis demonstrated that resveratrol decreased the expression levels of MMP-2, MMP-9, Fibronectin, α-SMA, P-PI3K, P-AKT, Smad2, Smad3, P-Smad2, P-Smad3, vimentin, Snail1, and Slug, as well as increased the expression levels of E-cadherin in MDA231 cells. In vivo, resveratrol inhibited lung metastasis in a mouse model bearing MDA231 human breast cancer xenografts without marked changes in body weight or liver and kidney function. These results indicate that resveratrol inhibits the migration of MDA231 cells by reversing TGF-β1-induced EMT and inhibits the lung metastasis of MDA231 human breast cancer in a xenograft-bearing mouse model.
79 citations
Cites background from "Resveratrol and its analogues: prom..."
...It is a natural compound that exists in more than 70 types of plants, such as hellebore, giant knotweed, grapes, and peanuts [12]....
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