Fighting Cancer with Red Wine? Molecular Mechanisms of Resveratrol

Abstract

Resveratrol, a red wine constituent, has been known for its cardioprotective effects. Recent data give ample evidence that resveratrol can act as a chemopreventive agent as well. Tumor initation, promotion, and progression are affected by resveratrol via multiple pathways, which are discussed in this review. Resveratrol has anti-inflammatory effects by counteracting NF-κ B and AP-1 transcription and can prevent bioactivation of procarcinogens by interacting with drug metabolizing enzymes. Furthermore, resveratrol exerts antioxidant activities, hence contributing to the prevention of tumor initiation. Growing or metastasizing carcinomas are inhibited by resveratrol through prevention of angiogenesis by inhibiting VEGF and matrix metalloproteases. Induction of apoptosis and cell cycle arrest, important mechanisms for cancer therapy, are stimulated by resveratrol through different mechanisms, e.g., activation of p53 and modulation of cell cycle proteins. Although there has been remarkable evidence for resveratrol as a potent chemopreventive agent in vitro, it seems that the low bioavailability of resveratrol in humans could interfere with a successful in vivo treatment. Nevertheless, resveratrol offers two major advantages over conventional chemotherapy. The cytotoxic effects of resveratrol on healthy cells can be neglected, and, as several pathways leading to chemotherapeutic effects are activated by resveratrol, chemoresistance-inducing mutations in cancer cells can be overcome.

Keywords:

• angiogenesis
• apoptosis
• bioavailability
• cancer
• chemoprevention
• inflammation
• resveratrol

Acknowledgments

The first three authors contributed equally.

Notes

1: 0.8μ Mresveratrolinredwine

2: 3.2μ Mresveratrolinredwine

3: average

4: notavailable

5: notdetectable

6: notquantifiable

a: 7,12-dimethylbenz[a]anthracene

b: N-nitrosobis(2-oxopropyl)amine

c: N-nitrosomethylbenzylamine

d: Azoxymethane

*: Resveratrol showed anticancer effects in previous cell culture experiment