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GADD153 mediates celecoxib-induced apoptosis in cervical cancer cells

Su-Hyeong Kim1, Chang-Il Hwang, Woong-Yang Park

  • 1Cancer Research Institute, Seoul National University College of Medicine, Chongno-Ku, Seoul 110-744, Korea.

Carcinogenesis
|April 7, 2006
PubMed

Insights

Celecoxib induces apoptosis in cervical cancer cells by upregulating GADD153 (growth arrest and DNA damage inducible gene). This transcription factor plays a key role in the cell death pathway, potentially by regulating proteins like Bak.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Celecoxib, a selective cyclooxygenase-2 inhibitor, exhibits anti-inflammatory properties and anticancer effects by inducing apoptosis.
  • Cervical cancer remains a significant global health concern, necessitating research into novel therapeutic mechanisms.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying celecoxib-induced apoptosis in cervical cancer cell lines.
  • To identify key genes and signaling pathways involved in celecoxib's apoptotic effects.

Main Methods:

  • Utilized cDNA microarray screening to identify differentially expressed genes in response to celecoxib treatment.
  • Employed siRNA-mediated gene silencing and exogenous gene expression to assess the role of GADD153.
  • Performed luciferase reporter gene assays and mRNA stability tests to investigate GADD153 regulation.
  • Analyzed signaling pathways, including NF-kappaB and Bak expression.

Main Results:

  • Celecoxib treatment significantly upregulated GADD153 (growth arrest and DNA damage inducible gene) expression in HeLa, CaSki, and C33A cervical cancer cells.
  • GADD153 silencing abrogated celecoxib-induced apoptosis, while its overexpression promoted apoptosis.
  • GADD153 expression was regulated at both transcriptional and post-transcriptional levels.
  • Celecoxib-induced apoptosis involved the upregulation of Bak, a proapoptotic protein, which was dependent on GADD153.

Conclusions:

  • GADD153 is a critical mediator of celecoxib-induced apoptosis in cervical cancer.
  • Celecoxib exerts its pro-apoptotic effects partly through the GADD153/Bak pathway.
  • These findings highlight GADD153 as a potential therapeutic target for cervical cancer treatment.

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