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GADD153-mediated anticancer effects of N-(4-hydroxyphenyl)retinamide on human hepatoma cells

Dae-Ghon Kim1, Kyung-Ran You, Ming-Jie Liu

  • 1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Institute for Molecular Biology and Genetics, Chonbuk National University Medical School and Hospital, Chonju, Chonbuk 561-712, South Korea. daeghon@moak.chonbuk.ac.kr

The Journal of Biological Chemistry
|July 26, 2002
PubMed

Insights

N-(4-hydroxyphenyl)retinamide (4HPR) induces cancer cell death via apoptosis. This study identifies GADD153 as a key gene overexpressed by 4HPR, mediating anticancer effects like growth arrest and apoptosis induction.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Biochemistry

Background:

  • N-(4-hydroxyphenyl)retinamide (4HPR) is a retinamide with potential anticancer applications.
  • The precise mechanism by which 4HPR induces apoptosis remains incompletely understood.
  • Identifying the specific genes involved in 4HPR-induced apoptosis is crucial for understanding its therapeutic potential.

Purpose of the Study:

  • To identify the specific gene(s) responsible for mediating apoptosis induced by 4HPR.
  • To elucidate the role of identified genes in 4HPR's anticancer effects.
  • To investigate the regulatory mechanisms of gene expression by 4HPR.

Main Methods:

  • Differential display-PCR was employed to identify genes responsive to 4HPR.
  • Gene expression analysis (transfection, mRNA stability) was performed in human hepatoma cell lines (Hep 3B, SK-HEP-1).
  • Functional studies involved ectopic GADD153 overexpression, antisense inhibition, and treatment with N-Acetyl-l-cysteine and Parthenolide.

Main Results:

  • GADD153 (growth arrest and DNA damage-inducible protein 153) was identified as preferentially expressed during 4HPR-induced apoptosis in cancer cells.
  • 4HPR regulates GADD153 expression at post-transcriptional and/or transcriptional levels depending on the cell line.
  • Overexpression of GADD153 in Hep 3B cells led to G1 cell cycle arrest and increased apoptosis, which was abrogated by GADD153 antisense or N-Acetyl-l-cysteine.

Conclusions:

  • GADD153 overexpression is a key mediator of 4HPR's anticancer effects, including apoptosis induction and growth arrest.
  • 4HPR's regulation of GADD153 occurs at multiple levels, contributing to its chemotherapeutic potential.
  • Targeting GADD153 may represent a viable strategy in 4HPR-based cancer therapy.

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