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Efavirenz induces DNA damage response pathway in lung cancer

Rahaba Marima1,2, Rodney Hull1, Zodwa Dlamini1,2

  • 1SA-MRC/UP Precision Prevention and Novel Drug Targets for HIV-Associated Cancers Extramural Unit, Pan African Cancer Research Institute, Faculty of Health Sciences, University of Pretoria, Hatfield 0028, South Africa.

Oncotarget
|October 28, 2020
PubMed

Insights

Efavirenz (EFV) alters cell-cycle gene expression in lung cancer cells, impacting pathways like ATM and p53. These findings suggest EFV possesses potential anti-tumour properties.

Area of Science:

  • Molecular biology
  • Cancer research
  • Pharmacology

Background:

  • Cell-cycle related genes are crucial for understanding efavirenz (EFV) effects in lung cancer.
  • Efavirenz is a drug with potential anti-tumour properties that warrants further investigation in lung cancer models.

Purpose of the Study:

  • To investigate the impact of efavirenz (EFV) on cell-cycle gene expression in human non-small cell lung carcinoma (A549) and normal lung fibroblast (MRC-5) cells.
  • To identify specific cell-cycle genes and signaling pathways affected by EFV treatment.

Main Methods:

  • Utilized 4', 6-diamidino-2-phenylindole (DAPI) staining to assess nuclear integrity changes induced by EFV.
  • Performed gene expression profiling using the human cell cycle PathwayFinder RT2 Profiler™ PCR Array to analyze 84 key cell-cycle genes.
  • Confirmed gene expression changes using quantitative real-time PCR (RT-qPCR) and Ingenuity Pathway Analysis (IPA).

Main Results:

  • EFV treatment caused significant changes (at least two-fold) in the expression of key cell-cycle genes, including MAD2L2, CASP3, and AURKB.
  • The ATM signaling pathway was upregulated in normal lung fibroblasts (MRC-5) following EFV treatment, leading to p53 upregulation.
  • The p53 signaling pathway was activated in lung cancer cells (A549) independently of the ATM pathway.

Conclusions:

  • EFV significantly alters cell-cycle gene expression in lung cancer and normal lung cells.
  • EFV's effects on cell-cycle and signaling pathways (ATM, p53) resemble those of ionizing radiation, indicating potential anti-tumour activity.
  • EFV demonstrates promise as a therapeutic agent for lung cancer, warranting further investigation.
Keywords:
DNA damage response pathwaycell cycledifferential gene expressionefavirenzlung cancer

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