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Iso-suillin-induced DNA damage leading to cell cycle arrest and apoptosis arised from p53 phosphorylation in

Yongxin Yan1, Shengjie Yao1, Zhiqiang Jia1

  • 1The Basic Medical College, Hebei Medical University, Shijiazhuang, 050017, PR China.

European Journal of Pharmacology
|July 4, 2021
PubMed

Insights

Iso-suillin, a natural compound, inhibits lung cancer cell growth by causing cell cycle arrest and apoptosis. This compound shows potential as a tumor growth inhibitor with no significant toxicity in preclinical studies.

Area of Science:

  • Natural Product Chemistry
  • Cancer Biology
  • Pharmacology

Background:

  • Iso-suillin, a secondary metabolite from Suillus flavus, has demonstrated anti-cancer properties.
  • Previous studies indicated iso-suillin induces cell cycle arrest and apoptosis in various cancer cell lines.

Purpose of the Study:

  • To investigate the anti-cancer mechanism of iso-suillin on human lung adenocarcinoma A549 cells.
  • To evaluate the in vitro and in vivo anti-tumor effects of iso-suillin.

Main Methods:

  • In vitro studies using A549 cells to assess proliferation, cell cycle, and apoptosis.
  • In vivo studies using an A549 xenograft mouse model to evaluate tumor growth inhibition.
  • Assessment of p53 phosphorylation at serines 15 and 20.
  • Evaluation of toxicity and body weight changes in vivo.

Main Results:

  • Iso-suillin significantly inhibited A549 cell proliferation by inducing early G1 phase arrest.
  • Iso-suillin promoted apoptosis in A549 cells in vitro.
  • Tumor growth and progression were suppressed in the A549 xenograft model.
  • p53 phosphorylation at serines 15 and 20 was identified as a key factor in iso-suillin's effects.
  • No significant toxicity was observed at a dose of 5 mg/kg.

Conclusions:

  • Iso-suillin exhibits potent in vitro and in vivo anti-tumor activity against lung adenocarcinoma.
  • The anti-cancer effects of iso-suillin are mediated through the induction of p53 phosphorylation, leading to cell cycle arrest and apoptosis.
  • Iso-suillin demonstrates potential as a therapeutic agent for lung cancer with a favorable safety profile.
Keywords:
ApoptosisG(0)/G(1) phase arrestIso-suillinXenograft tumorsp53 phosphorylation

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