NEW YORK—Resveratrol, known as an anti-cancer agent, suppressed UV-induced malignant tumor progression in mice and resveratrol-inhibited invasiveness of human A431 SCC cells appears to occur, in part, through the Akt-mediated downregulation of TGF-beta2, according to a study published in the Journal of Investigative Dermatology (2011;131:195-202).
Researchers have previously reported resveratrol arrests the growth of invasive human A431 squamous cell carcinoma (SCC) cells. In this study, they showed oral administration of resveratrol to highly tumor-susceptible p53+/-/SKH-1 mice markedly delayed UV-induced skin tumorigenesis and reduced the malignant conversion of benign papillomas to SCCs. Transforming growth factor-beta2 (TGF-beta2) was predominantly over expressed in UV-induced SCCs and its expression was diminished in resveratrol-treated SCCs/skin. In addition to the inhibition of TGF-beta2 expression, resveratrol increased the level of epithelial cadherin. This resveratrol -mediated TGF-beta2 downregulation led to the inhibition of both TGF-beta2/Smad-dependent and -independent pathways, and suppressed the invasiveness of A431 cells. Addition of TGF-beta2, but not TGF-beta1, rescued the resveratrol-mediated downregulation of p-extracellular signal-regulated kinases 1/2, p-Smad3, and alpha-smooth muscle actin. The protein kinase B (Akt) substrate cAMP response-binding protein (pCREB) trangascription factor is known to regulate TGF-beta2 expression, and resveratrol treatment decreased phosphorylation of Akt and pCREB. Expression of constitutively active Akt blocked resveratrol inhibition of CREB and TGF-beta2, and rescued resveratrol inhibition of cellular invasiveness.