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Resveratrol induces DNA damage-mediated cancer cell senescence through the DLC1-DYRK1A-EGFR axis

Fengqiu Ma1, Yan Ma1, Keke Liu1

  • 1Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan, 250014, Shandong, China. grli@sdnu.edu.cn.

Food & Function
|January 18, 2023
PubMed

Insights

Resveratrol induces cancer cell senescence by increasing reactive oxygen species (ROS) and enhancing tumor suppressor DLC1 expression. This triggers DNA damage via the DLC1-DYRK1A-EGFR pathway, offering potential for cancer prevention and treatment.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Senescence

Background:

  • Cell senescence is a key tumor suppression mechanism.
  • Resveratrol shows promise in cancer prevention and suppression.
  • The precise mechanism of resveratrol-induced cancer cell senescence remains unclear.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which resveratrol induces cancer cell senescence.
  • To investigate the role of the DLC1-DYRK1A-EGFR axis in resveratrol's anti-cancer effects.
  • To explore the potential of resveratrol in cancer prevention and adjuvant therapy.

Main Methods:

  • Assessed resveratrol's effects on cancer cell viability, colony formation, and senescence markers (SA-β-gal, p53, p21, LaminB).
  • Investigated resveratrol's impact on ROS generation, DLC1 expression, and the DYRK1A-EGFR signaling pathway.
  • Analyzed DNA damage markers (γH2AX, p-BRCA1, RAD51) and evaluated tumor growth in a xenograft model.

Main Results:

  • Resveratrol inhibited cancer cell proliferation and induced senescence, upregulating SA-β-gal activity and modulating key senescence markers.
  • Resveratrol increased ROS generation, leading to enhanced DLC1 expression, which inhibited the DYRK1A-EGFR axis and triggered DNA damage.
  • Resveratrol treatment reduced tumor volume in vivo, accompanied by increased SA-β-gal activity and DLC1 levels.

Conclusions:

  • Resveratrol induces DNA damage-mediated cancer cell senescence through the DLC1-DYRK1A-EGFR signaling pathway.
  • This study provides the first evidence of resveratrol's mechanism involving DNA damage and senescence induction via this specific axis.
  • Findings support resveratrol's potential as a food additive or adjuvant therapy for cancer prevention and treatment.

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