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IL-24 Inhibits Lung Cancer Growth by Suppressing GLI1 and Inducing DNA Damage

Janani Panneerselvam1,2, Akhil Srivastava1,2, Meghna Mehta2,3

  • 1Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.

Cancers
|December 1, 2019
PubMed

Insights

Interleukin-24 (IL-24) suppresses GLI1 expression and the DNA damage response (DDR) pathway in non-small cell lung cancer (NSCLC). This inhibition promotes cancer cell apoptosis, offering a potential therapeutic strategy for lung cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Aberrant GLI1 expression drives aggressive tumor behavior and survival by influencing the DNA damage response (DDR).
  • Interleukin-24 (IL-24) is a tumor suppressor with potential roles in modulating cancer pathways.

Purpose of the Study:

  • To investigate if IL-24 inhibits GLI1 and its associated DDR pathway in human non-small cell lung cancers (NSCLCs).

Main Methods:

  • Assessed GLI1 mRNA and protein levels following IL-24 treatment in NSCLC cells.
  • Utilized GLI1 reporter assays and mRNA studies to determine regulation mechanisms.
  • Evaluated DDR pathway activation via γ-H2AX foci and Comet assays.
  • Measured apoptosis markers (caspase-3, PARP activity) and employed GLI1 inhibition/overexpression studies.

Main Results:

  • IL-24 treatment significantly reduced GLI1 mRNA and protein expression in lung tumor cells, but not normal cells.
  • IL-24 mediated post-transcriptional regulation of GLI1, promoting mRNA degradation.
  • Suppression of GLI1 correlated with inhibited ATM-mediated DDR, increased DNA damage, and enhanced cancer cell apoptosis.
  • IL-24's anti-tumor effects were confirmed to be GLI-dependent and independent of the canonical hedgehog-signaling pathway.

Conclusions:

  • IL-24 treatment effectively reduces GLI1 expression and inhibits the DDR pathway in NSCLC.
  • IL-24 induces DNA damage and apoptosis in cancer cells, mediated by GLI1 suppression.
  • IL-24 represents a promising therapeutic agent for targeting GLI1 in lung cancer treatment.
Keywords:
DNA damageGLI1IL-24apoptosishedgehog signalinglung cancer

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