Different Concentrations Of Resveratrol Research Articles

Resveratrol induces mitochondria-mediated AIF and to a lesser extent caspase-9-dependent apoptosis in human lung adenocarcinoma ASTC-a-1 cells

Resveratrol (RV), a natural plant polyphenol widely present in foods such as grapes, wine, and peanuts, has an ability to inhibit various stages of carcinogenesis in vitro and in vivo. In this report, we explored the roles of intrinsic and extrinsic apoptotic pathways during RV-induced apoptosis in human lung adenocarcinoma (ASTC-a-1) cells. After exposure of cells to different concentrations of RV, we found that RV induced concentration-dependent apoptosis. Fluorometric substrates assay and western blotting (WB) analysis showed that caspase-8 was not activated, which was further verified by monitoring the cleavage of Bid to tBid using fluorescence resonance energy transfer (FRET) microscopy imaging inside single living cells, indicating that extrinsic apoptotic pathway was not involved in RV-induced apoptosis. In addition, inhibition of caspases-3 or -9 but not caspase-8 using the specific inhibitors of caspases modestly but significantly attenuated RV-induced apoptosis. Moreover, flow cytometry (FCM) analysis showed that RV treatment induced time-dependent loss of mitochondrial membrane potential (∆ψ(m)), in combination with the activation of caspases-3 and -9; we therefore concluded that RV-induced apoptosis involved the intrinsic apoptotic pathway. It is noteworthy that RV treatment induced translocation of AIF from mitochondria to nucleus in a time dependent manner, and that knockdown of AIF remarkably attenuated RV-induced apoptosis. Collectively, our findings demonstrate that RV induces caspase-8-independent apoptosis via AIF and to a lesser extent caspase-9-dependent mitochondrial pathway in ASTC-a-1 cells.

Resveratrol Potentiates Glucose-stimulated Insulin Secretion in INS-1E β-Cells and Human Islets through a SIRT1-dependent Mechanism

Resveratrol, a polyphenol compound, is known for its effects on energy homeostasis. With properties of energy sensors mediating effects of calorie restriction, sirtuins are targets of resveratrol. The mammalian sirtuin homolog SIRT1 is a protein deacetylase playing a role in glucose metabolism and islet function. Here, we investigated the effects of resveratrol and possible link with SIRT1 in β-cells. Insulinoma INS-1E cells and human islets were cultured with resveratrol before analyzing their physiological responses. Treatment of INS-1E cells for 24 h with 25 μM resveratrol resulted in marked potentiation of glucose-stimulated insulin secretion. This effect was associated with elevated glycolytic flux, resulting in increased glucose oxidation, ATP generation, and mitochondrial oxygen consumption. Such changes correlated with up-regulation of key genes for β-cell function, i.e. Glut2, glucokinase, Pdx-1, Hnf-1α, and Tfam. In human islets, chronic resveratrol treatment similarly increased both the glucose secretory response and expression of the same set of genes, eventually restoring the glucose response in islets obtained from one type 2 diabetic donor. Overexpression of Sirt1 in INS-1E cells potentiated resveratrol effects on insulin secretion. Conversely, inhibition of SIRT1 achieved either by expression of an inactive mutant or by using the EX-527 inhibitor, both abolished resveratrol effects on glucose responses. Treatment of INS-1E cells with EX-527 also prevented resveratrol-induced up-regulation of Glut2, glucokinase, Pdx-1, and Tfam. Resveratrol markedly enhanced the glucose response of INS-1E cells and human islets, even after removal of the compound from the medium. These effects were mediated by and fully dependent on active SIRT1, defining a new role for SIRT1 in the regulation of insulin secretion.

Resveratrol differentially modulates inflammatory responses of microglia and astrocytes

BackgroundInflammatory responses in the CNS mediated by activated glial cells play an important role in host-defense but are also involved in the development of neurodegenerative diseases. Resveratrol is a natural polyphenolic compound that has cardioprotective, anticancer and anti-inflammatory properties. We investigated the capacity of resveratrol to protect microglia and astrocyte from inflammatory insults and explored mechanisms underlying different inhibitory effects of resveratrol on microglia and astrocytes.MethodsA murine microglia cell line (N9), primary microglia, or astrocytes were stimulated by LPS with or without different concentrations of resveratrol. The expression and release of proinflammatory cytokines (TNF-α, IL-1β, IL-6, MCP-1) and iNOS/NO by the cells were measured by PCR/real-time PCR and ELISA, respectively. The phosphorylation of the MAP kinase superfamily was analyzed by western blotting, and activation of NF-κB and AP-1 was measured by luciferase reporter assay and/or electrophoretic mobility shift assay.ResultsWe found that LPS stimulated the expression of TNF-α, IL-1β, IL-6, MCP-1 and iNOS in murine microglia and astrocytes in which MAP kinases, NF-κB and AP-1 were differentially involved. Resveratrol inhibited LPS-induced expression and release of TNF-α, IL-6, MCP-1, and iNOS/NO in both cell types with more potency in microglia, and inhibited LPS-induced expression of IL-1β in microglia but not astrocytes. Resveratrol had no effect on LPS-stimulated phosphorylation of ERK1/2 and p38 in microglia and astrocytes, but slightly inhibited LPS-stimulated phosphorylation of JNK in astrocytes. Resveratrol inhibited LPS-induced NF-κB activation in both cell types, but inhibited AP-1 activation only in microglia.ConclusionThese results suggest that murine microglia and astrocytes produce proinflammatory cytokines and NO in response to LPS in a similar pattern with some differences in signaling molecules involved, and further suggest that resveratrol exerts anti-inflammatory effects in microglia and astrocytes by inhibiting different proinflammatory cytokines and key signaling molecules.

Abstract 3979: In vitro modeling of pharmacodynamics of resveratrol-induced anti-proliferation in breast cancer cells

Abstract We and others have shown that resveratrol, a naturally-occurring stilbene, induces p53-dependent apoptosis in human and animal cancer cell lines. The molecular basis of induction of apoptosis by resveratrol includes activation and nuclear translocation of mitogen-activated protein kinase (MAPK; ERK1/2) and MAPK-mediated Ser-15 phosphorylation of p53 (pSer15-p53). In this study, we used a newly developing perfusion bellows cell culture system to investigate resveratrol-induced apoptosis in the human estrogen receptor (ER)-negative breast cancer MDA-MB-231 cells. The cell culture system is a disposable bioreactor capable of high density cell culture for studies of anti-cancer drugs. Bellows-induced alternate flow of culture medium and air through porous matrices where cells are grown provides a relatively low shear, high aeration, foam-free culture environment. Medium level is raised and lowered to submerge and expose matrices to create a dynamic interface between air and media on the cell surface. Anchorage-dependent cells are grown on plastic flakes in the system; the flakes facilitate harvesting of whole cells for analysis. After 6 days incubation, the IC50 of resveratrol-induced apoptosis was 0.1 μM. Short term incubation with 10 μM resveratrol for 6 days inhibited cell proliferation by 75%. Using an injection system to pump media with different concentrations of resveratrol (0.5 μM to 100 μM), we were able to reproduce the resveratrol-induced anti-proliferation effect in the perfusion bellows culture system. Incubating the cells in either acidic or alkaline condition did not affect anti-proliferation induced by resveratrol. The effect of resveratrol-induced apoptosis is based on increasing transcription of pro-apoptotic p53-dependent genes such as PIG3, c-fos, c-jun and BAD. The aim of the present study is to establish the pharmacodynamics of resveratrol in the suppression or elimination of human breast cancer cells. With the use of the perfusion bellows cell culture system we will provide an efficient, convenient and financially beneficial method for determining optimal regimens for the effective suppression and elimination of these cancer cells. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3979.

Resveratrol이 포도주의 관능평가에 미치는 영향

Dept. of Microbial Engineering, Konkuk University, Seoul 143-701, Korea AbstractIn this study, effect of resveratrol concentration on wine taste was investigated. Content of resveratrol in 14 different wines were quantified using HPLC. The resveratrol concentrations in the Australian wine samples (grape species: Syrah) with 3 vintage years were analyzed and different concentrations of resveratrol were observed (2.89~3.84 mg/L). Variation in wine grape species with the same wine manufacturer (Chile, 2006) and variation in different manufacturing country of origin with same wine grape species (Cabernet Sauvignon, 2006) also produced the variations in resveratrol concentration. The preference analysis (color, aroma, taste, astringency and overall acceptability) of the sample wines were determined by 15 panelists using 5-point hedonic scale. When the analysis results of the resveratrol concentrations in the sample wines were compared with the preference analysis of sample wines, the resveratrol concentration in the wine produced the positive effects in the wine preference analysis in the factors of aroma, taste and color.Key words: resveratrol, wine, wine analysis, HPLC, wine preference test

Resveratrol increases sensitivity of CNE2 cells to chemotherapeutic drugs under hypoxia

To explore the sensitization effects of resveratrol on CNE2 nasopharyngeal carcinoma cell line with hypoxia-induced chemotherapy resistance and the potential mechanism. Human CNE2 nasopharyngeal carcinoma cell line was cultured under hypoxic conditions (37 degrees centigrade, 5% CO(2), 2% O(2)) in vitro. The cultured cells were treated with different concentrations of resveratrol for 48 h. Reversal fold (RF) of reseratrol to chemotherapeutic drugs in CNE2 cells was measured by methyl thiazolyl tetrazolium (MTT) assay. Apoptotic rate of CNE2 cells was observed by flow cytometry. Reverse transcription-polymerase chain reaction (RT-PCR) method and Western blotting were used to investigate the expressions of multidrug resistance gene 1 (mdr1), multidrug resistance-associated protein 1 (MRP1) and hypoxia inducible factor 1alpha (HIF-1alpha) in CNE2 cells. Resveratrol combined with chemotherapeutics produced a synergistic effect. The RF of 200 micromol/L resveratrol to paclitaxel was 2.58. Combined with paclitaxel, 25, 50, 100 and 200 micromol/L of resveratrol increased the apoptotic rate of CNE2 cells from (22.14+/-1.09)% to (23.24+/-1.37)%, (27.57+/-2.01)%, and (30.36+/-2.31)%, respectively. Resveratrol could down-regulate the expressions of HIF-1alpha, mdr1 and MRP1 significantly. After being treated with resveratrol at different concentrations separately, the expressions of HIF-1alpha, mdr1 and MRP1 in CNE2 cells decreased significantly as compared with paclitaxel alone or paclitaxel plus verapamil (P<0.01). Resveratrol can enhance the sensitivity of CNE2 cells to chemotherapeutic drugs under hypoxia. The potential mechanism is partly attributed to inhibiting the gene expressions of HIF-1alpha, mdr1 and MRP1.

Resveratrol Protects Auditory Hair Cells from Gentamicin Toxicity

Resveratrol is a naturally occurring polyphenol that is synthesized by a variety of plant species. It is abundant in grapes and grape products (e.g., red wine). Resveratrol has demonstrated reactive oxygen species (ROS) scavenger activity, and it has been linked to nuclear factor-kappa B (NF-kappaB) activity. We recently demonstrated that NF-kappaB is important to the survival of immature mammalian hair cells. Therefore, we undertook an in vitro experiment to determine if resveratrol is able to exert some protective influence against gentamicin-induced damage to and death of auditory hair cells. To accomplish this, we dissected the organ of Corti (OC) from newborn Sprague-Dawley rats and cultured the OCs in medium overnight for recovery. We treated two groups of OC explants with different concentrations of resveratrol plus gentamicin for 24 hours; for comparison and control purposes, we also treated a group of explants with gentamicin only and we left a group untreated. We found that resveratrol in both concentrations had a moderate but statistically significant protective effect against gentamicin-induced toxicity in vitro.

Resveratrol induces apoptosis in human osteosarcoma MG63 cells

OBJECTIVE To investigate apoptosis in human osteosarcoma MG63 cells induced by resveratrol and the molecular mechanism involved. METHODS MG63 cells were treated with different concentrations of resveratrol and transmission electron microscopy was used to observe morphological changes occurring in apoptosis. The MTT method was used to determine the inhibitory rate and flow cytometry was used to assess apoptosis and to analyze the expression of the p21 cip1/WAF1 and survivin proteins; the expression of p21 cip1/WAF1 and survivin mRNAs was analyzed by the reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS After resveratrol treatment, the growth of the MG63 cells was significantly inhibited in a time- and dose-dependent fashion. By transmission electron microscopy, the cells displayed morphological changes characteristic of apoptosis, including formation of cytoplasmic vacuoles, chromatin condensation and margination. Flow cytometry showed that the growth of the cells was inhibited after resveratrol (10 mg/L and 20 mg/L) treatment. The inhibitory rates were (11.9 ± 0.63)% and (19.7 ± 0.88)% respectively. The quantity of treated cells in G0 /G1 transition was increased, but the number in the S phase and G2/M transition was decreased. A subdiploid peak was observed. The expression of p21cip1/WAF1 was up-regulated while survivin was down-regulated. CONCLUSION Resveratrol can inhibit growth and induce apoptosis of MG63 cells. Its molecular mechanism might be related to modulation of survivin and p21cip1/WAF1 expression.

Resveratrol reestablishes spermatogenesis after testicular injury in rats caused by 2,5-hexanedione

Environmental toxins can destroy the physiological process of spermatogenesis and even lead to male infertility. Resveratrol (RES) is a natural phytoalexin with a wide range of biological activities. Some recent researches have demonstrated that RES can increase sperm output and protect sperm from apoptosis caused by physical damage. However, there is no evidence indicating that it can also exhibit a similar activity in testis injury caused by environmental toxins. This study was designed to evaluate the protective effect of resveratrol on testis damaged by environmental toxins and to elucidate the possible mechanism of its protective effect. In this study 2, 5-hexanedione (2, 5-HD) was used as the injury agent. Forty male SD rats were randomly divided into 5 groups. During the first 5 weeks, group A was raised normally, groups B, C, D and E were exposed to 1% 2, 5-HD; during the following 9 weeks, group C, D, E received intragastric administration of different concentrations of resveratrol (20 mg x kg(-1) x d(-1), 40 mg x kg(-1) x d(-1) and 80 mg x kg(-1) x d(-1)), while groups A and B were treated by carboxymethylcellulose. Physical signs, body weight gain and testis weight were comparatively observed. Numbers and diameters of seminiferous tubules were analyzed following HE staining. In addition, expression of the c-kit protein and gene in spermatogenic cells in every group was detected with immunohistochemistry, Western blot or RT-PCR. The 2, 5-HD treatment resulted in physical signs that became worse and in emarciated testis. HE staining and immunohistochemistry showed that seminiferous tubules became emarcid, obsolete spermatogonia being stagnant and expression of c-kit protein being depressed. After oral administration of resveratrol, the 2, 5-HD-induced physical signs were improved and close to the normal rats. The gain of body weight increased (P < 0.01). The recovery of testis weight was significant (P < 0.01). At the histological level, the seminiferous epithelia began to differentiate (P < 0.01); and even the physiological process of spermatogenesis restarted. Moreover, expression of c-kit protein and gene function resumed, although its expression remained different from the normal group. The diameter of and number of seminiferous tubules and the expression level of c-kit protein and gene activity were much closer to the normal group with increased doses of the resveratrol through oral administration. Resveratrol could ameliorate markedly the dyszoospermia induced by 2, 5-HD and induce spermatogenesis. The expression of c-kit, which is a specific marker protein of spermatogenic cell membranes, could be regulated by resveratrol.

Effects of resveratrol on matrix metalloproteinase-9 expression in hepatoma cells

To observe the effects of resveratrol on proliferation of human hepatocellular carcinoma cell line SMMC-7721 cells and expression of matrix metalloproteinase-9 (MMP-9) in vitro. SMMC-7721 cells were treated with different concentrations of resveratrol for 24, 48 and 72 h, respectively. The effect of resveratrol on proliferation of SMMC-7721 cells was assessed with methyl thiazolyl tetrazolium (MTT). The expression of MMP-9 mRNA was determined by reverse transcription polymerase chain reaction (RT-PCR). MMP-9 protein was identified by Western blot analysis. Resveratrol could inhibit the proliferation of SMMC-7721 cells with dose- and time-dependent effects. Moreover, both MMP-9 mRNA expression and MMP-9 protein production were markedly reduced after resveratrol treatment. Resveratrol can inhibit the proliferation of SMMC-7721 cells and down-regulate MMP-9 expression. It is presumed that resveratrol may suppress the invasion and metastasis of hepatocellular carcinoma.

Resveratrol potently reduces prostaglandin E2production and free radical formation in lipopolysaccharide-activated primary rat microglia

BackgroundNeuroinflammatory responses are triggered by diverse ethiologies and can provide either beneficial or harmful results. Microglial cells are the major cell type involved in neuroinflammation, releasing several mediators, which contribute to the neuronal demise in several diseases including cerebral ischemia and neurodegenerative disorders. Attenuation of microglial activation has been shown to confer protection against different types of brain injury. Recent evidence suggests that resveratrol has anti-inflammatory and potent antioxidant properties. It has been also shown that resveratrol is a potent inhibitor of cyclooxygenase (COX)-1 activity. Previous findings have demonstrated that this compound is able to reduce neuronal injury in different models, both in vitro and in vivo. The aim of this study was to examine whether resveratrol is able to reduce prostaglandin E2 (PGE2) and 8-iso-prostaglandin F2α (8-iso-PGF2α) production by lipopolysaccharide (LPS)-activated primary rat microglia.MethodsPrimary microglial cell cultures were prepared from cerebral cortices of neonatal rats. Microglial cells were stimulated with 10 ng/ml of LPS in the presence or absence of different concentrations of resveratrol (1–50 μM). After 24 h incubation, culture media were collected to measure the production of PGE2 and 8-iso-PGF2α using enzyme immunoassays. Protein levels of COX-1, COX-2 and microsomal prostaglandin E synthase-1 (mPGES-1) were studied by Western blotting after 24 h of incubation with LPS. Expression of mPGES-1 at the mRNA level was investigated using reverse transcription-polymerase chain reaction (RT-PCR) analysis.ResultsOur results indicate that resveratrol potently reduced LPS-induced PGE2 synthesis and the formation of 8-iso-PGF2α, a measure of free radical production. Interestingly, resveratrol dose-dependently reduced the expression (mRNA and protein) of mPGES-1, which is a key enzyme responsible for the synthesis of PGE2 by activated microglia, whereas resveratrol did not affect the expression of COX-2. Resveratrol is therefore the first known inhibitor which specifically prevents mPGES-1 expression without affecting COX-2 levels. Another important observation of the present study is that other COX-1 selective inhibitors (SC-560 and Valeroyl Salicylate) potently reduced PGE2 and 8-iso-PGF2α production by LPS-activated microglia.ConclusionThese findings suggest that the naturally occurring polyphenol resveratrol is able to reduce microglial activation, an effect that might help to explain its neuroprotective effects in several in vivo models of brain injury.

Chronic Treatment with Resveratrol Induces Redox Stress- and Ataxia Telangiectasia-mutated (ATM)-dependent Senescence in p53-positive Cancer Cells

The induction of senescence, an irreversible growth arrest, in cancer cells is regarded as a mean to halt tumor progression. The phytoalexin resveratrol (RV) is known to possess a variety of cancer-preventive, -therapeutic, and -chemosensitizing properties. We report here that chronic treatment with RV in a subapoptotic concentration induces senescence-like growth arrest in tumor cells. In contrast to the widely accepted antioxidant property of RV, we demonstrate that one causative stimulus for senescence induction by chronic RV is an increased level of reactive oxygen species (ROS). The ROS formed upon RV exposure include hydrogen peroxide and superoxide and originate largely from mitochondria. Consistently, co-incubation with the antioxidant N-acetyl cysteine interfered with RV-mediated reactivation of the senescence program. Molecular mediators on the way from increased ROS levels to the observed growth arrest include p38 MAPK, p53, and p21. Moreover, we provide evidence that RV-initiated replication stress, apparent by activation of the ataxia telangiectasia-mutated kinase pathway, is associated with increased ROS levels and senescence induction. This is the first report linking cell cycle effects with a pro-oxidant and pro-senescent effect of RV in cancer cells.

Effect of Resveratrol on NF-κB Activity in Rat Peritoneal Macrophages

This study was to investigate the inhibitive effect of resveratrol (RESV) on nuclear factor kappa B (NF-kappaB) expression and activity induced by lipopolysaccharide (LPS) in rat peritoneal macrophages (PMA). Male Sprague-Dawley (SD) rats were randomly divided into 7 groups, including control group, LPS group and RESV I-V group. In the LPS group, PMA were incubated in DMEM containing LPS (10 microg/ml), whereas in control group, PMA were incubated in DMEM only. In the RESV I-V groups, PMA were incubated in DMEM containing LPS (10 microg/ml) and different concentrations of RESV. After 24 hours of incubation, NF-kappaB activity in PMA, and the levels of tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1) and nitric oxide (NO) in the culture medium were measured. In the concentrations of 1.25-5 microg/ml, RESV had a dose- dependent inhibitive effect on NF-kappaB activity in PMA as well as the expressions of TNF-alpha, IL-1 and NO in the culture medium contrasted with the LPS group. There was no significant difference in the levels of these pro-inflammatory factors between the groups of 5 microg/ml and 10 microg/ml RESV. In conclusion, RESV has the potential for the future application of preventing inflammatory diseases involving PMA.

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

To study the antitumor and immunomodulatory activity of resveratrol on experimentally implanted tumor of H22 in Balb/c mice. The cytotoxicity of peritoneal macrophages (Mphi) against H22 cells was measured by the radioactivity of ((3)H)TdR assay, mice with H22 tumor were injected with different concentrations of resveratrol, and the inhibitory rates were calculated and IgG contents were determined by single immunodiffusion method. the plaque forming cell (PFC) was measured by improved Cunningham method, the levels of serum tumor necrosis factor-alpha (TNF-alpha) were measured by cytotoxic assay against L929 cells. Resveratrol 2.5 mg x L(-1), 5.0 mg x L(-1), 10.0 mg x L(-1), 20.0 mg x L(-1) (E:T=10:1, 20:1) promoted the cytotoxicity of Mphi against H22 cells. Resveratrol ip 500 mg x kg(-1), 1 000 mg x kg(-1) and 1,500 mg x kg(-1) could curb the growth of the implanted tumor of H22 in mice. The inhibitory rates were 31.5 %, 45.6 % and 48.7 %, respectively (P<0.05), which could raise the level of serum IgG and PFC response to sheep red blood cell. Resveratrol 1,000 mg x kg(-1) and 1,500 mg x kg(-1) and BCG 200 mg x kg(-1) ip could increase the production of serum TNF-alpha in mice H22 tumor. However, the effect of resveratrol was insignificant (P>0.05). 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.

Differential Effects on Growth, Cell Cycle Arrest, and Induction of Apoptosis by Resveratrol in Human Prostate Cancer Cell Lines

Epidemiologic studies have suggested that nutrition plays an important role in carcinogenesis and that 30% of cancer morbidity and mortality can potentially be prevented with proper adjustment of diets. Resveratrol, a polyphenol present in red wines and a variety of human foods, has recently been reported to exhibit chemopreventive properties when tested in a mouse skin cancer model system. In this study, we investigated the effects of resveratrol on growth, induction of apoptosis, and modulation of prostate-specific gene expression using cultured prostate cancer cells that mimic the initial (hormone-sensitive) and advanced (hormone-refractory) stages of prostate carcinoma. Androgen-responsive LNCaP and androgen-nonresponsive DU-145, PC-3, and JCA-1 human prostate cancer cells were cultured with different concentrations of resveratrol (2.5 × 10−5–10−7M). Cell growth, cell cycle distribution, and apoptosis were determined. Addition of 2.5 × 10−5M resveratrol led to a substantial decrease in growth of LNCaP and in PC-3 and DU-145 cells, but only had a modest inhibitory effect on proliferation of JCA-1 cells. Flow cytometric analysis showed resveratrol to partially disrupt G1/S transition in all three androgen-nonresponsive cell lines, but had no effect in the androgen-responsive LNCaP cells. In difference to the androgen-nonresponsive prostate cancer cells however, resveratrol causes a significant percentage of LNCaP cells to undergo apoptosis and significantly lowers both intracellular and secreted prostate-specific antigen (PSA) levels without affecting the expression of the androgen receptor (AR). These results suggest that resveratrol negatively modulates prostate cancer cell growth, by affecting mitogenesis as well as inducing apoptosis, in a prostate cell-type-specific manner. Resveratrol also regulates PSA gene expression by an AR-independent mechanism.