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Isorhapontigenin (ISO) inhibited cell transformation by inducing G0/G1 phase arrest via increasing MKP-1 mRNA

Guangxun Gao1, Liang Chen, Jingxia Li

  • 1Nelson Institute of Environmental Medicine, New York University School of Medicine,Tuxedo, NY, USA.

Oncotarget
|May 7, 2014
PubMed

Insights

Isorhapontigenin (ISO), a Chinese herb isolate, shows promising cancer chemopreventive effects by inducing cell-cycle arrest and inhibiting cell transformation. ISO achieves this by upregulating MKP-1 mRNA stability, distinct from its cancer therapeutic mechanisms.

Area of Science:

  • Phytochemistry
  • Cancer Biology
  • Molecular Pharmacology

Background:

  • The chemopreventive potential of isorhapontigenin (ISO), a novel isolate from Chinese herbs, remains unexplored.
  • Understanding the molecular mechanisms of ISO's activity is crucial for its therapeutic development.

Purpose of the Study:

  • To investigate the cancer chemopreventive properties of ISO.
  • To elucidate the underlying molecular mechanisms of ISO's anti-cancer activity.

Main Methods:

  • Soft Agar assay to assess cell transformation inhibition.
  • Cell-cycle analysis to evaluate cell-cycle arrest.
  • Western blotting and quantitative PCR to analyze protein and gene expression.
  • Gene knockdown and ectopic expression studies to confirm molecular targets.

Main Results:

  • ISO significantly inhibited TPA/EGF-induced Cl41 cell transformation and induced G0/G1 cell-cycle arrest without cytotoxicity.
  • ISO downregulated cyclin D1 expression at the transcriptional level by targeting JNK/C-Jun/AP-1 activation.
  • ISO upregulated MKP-1 expression via increased mRNA stability and MKK7 deactivation, which was critical for its observed effects.

Conclusions:

  • ISO demonstrates significant cancer chemopreventive potential by upregulating MKP-1 mRNA stability, leading to cell-cycle arrest and inhibition of cell transformation.
  • These findings highlight a distinct mechanism for ISO's chemopreventive action compared to its cancer therapeutic effects.

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