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Lovastatin protects keratinocytes from DNA damage-related pro-apoptotic stress responses stimulated by anticancer

Verena Ziegler1, Anne Albers1, Gerhard Fritz1

  • 1Institute of Toxicology, Medical Faculty of the Heinrich Heine University Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, Germany.

Biochimica Et Biophysica Acta
|February 16, 2016
PubMed
Abstract

Insights

Lovastatin protects skin cells from DNA damage caused by cancer therapies like radiation and doxorubicin. This finding suggests statins may help prevent oral mucositis, a common side effect.

Area of Science:

  • Oncology
  • Pharmacology
  • Cell Biology

Background:

  • Oral mucositis (OM) is a severe side effect of cancer treatments like ionizing radiation (IR) and doxorubicin (Doxo).
  • DNA damage in keratinocytes is a key factor in OM development.
  • Identifying protective agents for keratinocytes is crucial.

Purpose of the Study:

  • To investigate the protective effects of lovastatin against IR- and Doxo-induced damage in human keratinocytes.
  • To explore lovastatin's impact on cell death, proliferation, and DNA damage response (DDR) pathways.

Main Methods:

  • Human keratinocytes were treated with IR and Doxo, with and without lovastatin.
  • Assessed cell death, proliferation, and DNA damage markers.
  • Investigated the activation of key DDR kinases (ATR, Chk1).

Main Results:

  • Lovastatin reduced apoptosis and DNA damage induced by IR and Doxo.
  • Lovastatin inhibited ATR/Chk1 kinase activation, suggesting antagonism of replicative stress responses.
  • Cytoprotective effects were observed in both proliferating and non-proliferating keratinocytes, indicating multiple mechanisms.

Conclusions:

  • Lovastatin demonstrates significant cytoprotective and genoprotective effects on keratinocytes against OM-inducing agents.
  • These findings support further research into statins for OM prevention in cancer patients.
Keywords:
AnthracyclinesCell deathDNA damage response (DDR)DNA repairIonizing radiationKeratinocytesOral mucositisStatins

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