Cancer Prevention and Treatment with Resveratrol: From Rodent Studies to Clinical Trials

Abstract

Resveratrol (3,4′,5-trihydroxy-trans-stilbene) is a dietary polyphenol derived from grapes, berries, peanuts, and other plant sources. During the last decade, resveratrol has been shown to possess a fascinating spectrum of pharmacologic properties. Multiple biochemical and molecular actions seem to contribute to resveratrol effects against precancerous or cancer cells. Resveratrol affects all three discrete stages of carcinogenesis (initiation, promotion, and progression) by modulating signal transduction pathways that control cell division and growth, apoptosis, inflammation, angiogenesis, and metastasis. The anticancer property of resveratrol has been supported by its ability to inhibit proliferation of a wide variety of human tumor cells in vitro. These in vitro data have led to numerous preclinical animal studies to evaluate the potential of this drug for cancer chemoprevention and chemotherapy. This review provides concise, comprehensive data from preclinical in vivo studies in various rodent models of human cancers, highlighting the related mechanisms of action. Bioavailability, pharmacokinetic, and potential toxicity studies of resveratrol in humans and ongoing interventional clinical trials are also presented. The conclusion describes directions for future resveratrol research to establish its activity and utility as a human cancer preventive and therapeutic drug.

Resveratrol Exerts Differential Effects in Vitro and in Vivo against Ovarian Cancer Cells

“…Since resveratrol is primarily metabolized in the liver, the gastrointestinal bioavailability would be significantly thus explaining the demonstrated efficacy of resveratrol in gastrointestinal cancers, including liver cancer (reviewed by Bishayee, 2009). The low circulating levels of drug reaching the ovarian cancer tissue may be too low to yield a therapeutic threshold to achieve an effect in the current study.…”

“…Review of the recent literature provides a convincing body of evidence demonstrating resveratrol to have numerous antitumor properties including the ability to decrease cell proliferation, induce apoptosis, and inhibit angiogenesis and tumor growth by mediating a variety of cellular pathways (Bishayee, 2009;Athar et al, 2009;Weng & Yen, 2012). These effects have been documented in numerous types of cancer cells from skin, breast, ovary, prostate, gastrointestinal tract and lung (Aggarwal et al, 2004;Kundu & Surh, 2008).…”

“…Although NuTu-19 ovarian cancer cells were shown to be apoptosis resistant, these cells can be induced to undergo apoptosis when tumor-associated cellular mechanisms are stabilized (Feki et al, 2005;Brard et al, 2006). Since resveratrol mediates effects on a range of pathways (Athar et al, 2009;Bishayee, 2009;Weng & Yen, 2012), cellular stabilization and apoptosis was expected. However, regions of ovarian cancer from control and resveratrol-treated animals showed no detectable difference in fluorescence compared to the negative controls, indicating the absence of resveratrol-mediated apoptosis in the NuTu-19 cells in an in vivo condition.…”

“…Because of its high concentration in grape skin, a significant amount of resveratrol is present in wines, especially red wines, and it is considered to be responsible for the beneficial effects of red wines against coronary heart disease (Fremont, 2000). Resveratrol is gaining tremendous importance as it possesses cancer preventive as well as anticancer activities in various biological systems (reviewed by Bishayee, 2009). In animal studies, resveratrol prevents or delays the development of skin (Jang et al, 1997), mammary (Banerjee et al, 2002) and prostate (Harper et al, 2007) tumors as well as blocks or suppresses esophageal (Li et al, 2002), gastric (Zhou et al, 2005), small intestinal (Schneider et al, 2001), colonic (Tessitore at al., 2000;Sengottuvelan et al, 2006) pancreatic (Harikumar et al, 2010), and hepatic (Bishayee & Dhir, 2009) tumorigenesis.…”

Plant-derived anticancer agents: a promising treatment for bone metastasis

“…49 Resveratrol has been associated with beneficial effects in preclinical animal studies in various models of cancer and other diseases such as diabetes, arthritis, neurodegenerative and pulmonary diseases, as well as bone loss. 50 In vivo studies of mice with DMBA (dimethylbenz[a]anthracene)-induced mammary tumors showed that the addition of resveratrol in the diet reduces the incidence and number of tumors. 51 Treatment with resveratrol decreased in tumors the expression of COX-2, matrix metalloprotease (MMP-9) and NF-kB genes associated with tumor growth and invasion.…”