Biological activity of piceatannol: leaving the shadow of resveratrol

Mutat Res. 2012 Jan-Mar;750(1):60-82. doi: 10.1016/j.mrrev.2011.11.001.

Abstract

Resveratrol (3,4',5-trans-trihydroxystilbene), a naturally occurring stilbene, is considered to have a number of beneficial effects, including anticancer, anti-aethrogenic, anti-oxidative, anti-inflammatory, anti-microbial and estrogenic activity. Piceatannol (3, 3', 4, 5'-trans-trihydroxystilbene), a naturally occurring hydroxylated analogue of resveratrol, is less studied than resveratrol but displays a wide spectrum of biological activity. Piceatannol has been found in various plants, including grapes, passion fruit, white tea, and Japanese knotweed. Besides antioxidative effects, piceatannol exhibits potential anticancer properties as suggested by its ability to suppress proliferation of a wide variety of tumor cells, including leukemia, lymphoma; cancers of the breast, prostate, colon and melanoma. The growth-inhibitory and proapoptotic effects of piceatannol are mediated through cell-cycle arrest; upregulation of Bid, Bax. Bik, Bok, Fas: P21(WAF1) down-regulation of Bcl-xL; BCL-2, clAP, activation of caspases (-3, -7,- 8, -9), loss of mitochondrial potential, and release of cytochrome c. Piceatannol has been shown to suppress the activation of some transcription factors, including NF-kappaB, which plays a central role as a transcriptional regulator in response to cellular stress caused by free radicals, ultraviolet irradiation, cytokines, or microbial antigens. Piceatannol also inhibits JAK-1, which is a key member of the STAT pathway that is crucial in controlling cellular activities in response to extracellular cytokines and is a COX-2-inducible enzyme involved in inflammation and carcinogenesis. Although piceatannol has been shown to induce apoptosis in cancer cells, there are examples of its anti-apoptotic pro-proliferative activity. Piceatannol inhibits Syk kinase, which plays a crucial role in the coordination of immune recognition receptors and orchestrates multiple downstream signaling pathways in various hematopoietic cells. Piceatannol also binds estrogen receptors and stimulates growth of estrogen-dependent cancer cells. Piceatannol is rapidly metabolized in the liver and is converted mainly to a glucuronide conjugate; however, sulfation is also possible, based on in vitro studies. The pharmacological properties of piceatannol, especially its antitumor, antioxidant, and anti-inflammatory activities, suggests that piceatannol might be a potentially useful nutritional and pharmacological biomolecule; however, more data are needed on its bioavailability and toxicity in humans.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anticarcinogenic Agents / pharmacology
  • Antimutagenic Agents / pharmacology
  • Antineoplastic Agents / pharmacology
  • Antioxidants / pharmacology
  • Cell Proliferation / drug effects
  • Humans
  • Mice
  • Rats
  • Resveratrol
  • Stilbenes / chemistry
  • Stilbenes / metabolism
  • Stilbenes / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Anticarcinogenic Agents
  • Antimutagenic Agents
  • Antineoplastic Agents
  • Antioxidants
  • Stilbenes
  • 3,3',4,5'-tetrahydroxystilbene
  • Resveratrol