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Published on: October 27, 2020

Resveratrol targets transforming growth factor-β2 signaling to block UV-induced tumor progression

Kwang Ho Kim1, Jung Ho Back, Yucui Zhu

  • 1Department of Dermatology, Columbia University Medical Center, Irving Cancer Research Center, New York, New York, USA.

The Journal of Investigative Dermatology
|August 20, 2010
PubMed

Insights

Resveratrol (RES) effectively suppresses UV-induced skin cancer progression in mice and human cells. It works by downregulating transforming growth factor-beta 2 (TGF-β2) via the Akt pathway, reducing tumor invasiveness.

Area of Science:

  • Oncology
  • Dermatology
  • Molecular Biology

Background:

  • Resveratrol (RES) is recognized for its anti-cancer properties.
  • Previous studies demonstrated RES's ability to inhibit invasive human squamous cell carcinoma (SCC) cell growth.
  • UV radiation is a known inducer of skin tumorigenesis.

Purpose of the Study:

  • To investigate the efficacy of oral Resveratrol (RES) in preventing UV-induced skin cancer in mice.
  • To elucidate the molecular mechanisms underlying RES's anti-cancer effects, particularly its impact on transforming growth factor-beta 2 (TGF-β2) and cell invasiveness.

Main Methods:

  • Oral administration of RES to p53(+/-)/SKH-1 mice.
  • Induction of skin tumors using UV radiation.
  • Analysis of TGF-β2 and epithelial cadherin expression in tumor tissues.
  • Investigation of signaling pathways including Akt, CREB, and Smad.
  • In vitro studies using A431 SCC cells to assess RES's effect on invasiveness.

Main Results:

  • RES administration significantly delayed UV-induced skin tumorigenesis and reduced the conversion of benign papillomas to SCCs in mice.
  • RES treatment diminished the overexpression of TGF-β2 in UV-induced SCCs and increased epithelial cadherin levels.
  • RES suppressed SCC cell invasiveness by downregulating TGF-β2 through the Akt/CREB pathway, affecting both TGF-β2/Smad-dependent and -independent pathways.

Conclusions:

  • Resveratrol demonstrates significant potential in suppressing UV-induced skin malignant progression.
  • The Akt-mediated downregulation of TGF-β2 is a key mechanism by which RES inhibits SCC cell invasiveness.
  • RES represents a promising therapeutic agent for preventing and treating skin cancers.

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