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Anti-Proliferative Effect of Statins Is Mediated by DNMT1 Inhibition and p21 Expression in OSCC Cells

Rachmad Anres Dongoran1,2, Kai-Hung Wang3, Tsung-Jen Lin1

  • 1Ph.D. Program in Pharmacology and Toxicology, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan.

Cancers
|August 1, 2020
PubMed

Insights

Statins inhibit oral cancer cell growth by causing cell cycle arrest. This effect is linked to reduced DNA methyltransferase 1 (DNMT1) and increased p21 expression, offering potential therapeutic strategies for oral squamous cell carcinoma (OSCC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Statins, HMG-CoA reductase inhibitors, are known for cholesterol reduction.
  • Emerging evidence suggests statins possess anti-cancer properties across various malignancies.

Purpose of the Study:

  • To investigate the anti-proliferative effects of statins on oral squamous cell carcinoma (OSCC) cells.
  • To elucidate the molecular mechanisms underlying statin-induced growth inhibition in OSCC.

Main Methods:

  • Treatment of three OSCC cell lines with cerivastatin and simvastatin.
  • Analysis of cell proliferation, cell cycle distribution (G0/G1 arrest), and expression levels of p21, cyclin-dependent kinases (CDK2, CDK4, CDK6), and DNA methyltransferase 1 (DNMT1).

Main Results:

  • Statins demonstrated a dose-dependent inhibition of OSCC cell proliferation.
  • Statin treatment induced G0/G1 cell cycle arrest, accompanied by p21 upregulation and CDK2, CDK4, CDK6 downregulation.
  • Statins significantly inhibited DNMT1 expression and concurrently promoted p21 expression.

Conclusions:

  • The anti-proliferative effects of statins in OSCC are mediated by the suppression of DNMT1 expression.
  • This suppression leads to increased p21 expression, resulting in G0/G1 cell cycle arrest and growth inhibition in OSCC cells.
Keywords:
DNMT1G0/G1 cell cycle arrestoral squamous cell carcinomap21statins

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