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Anticancer effect of involucrasin A on colorectal cancer cells by modulating the Akt/MDM2/p53 pathway

Chengming Wei1, Jingjing Du1, Yunfu Shen1

  • 1State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, SAR 999078, P.R. China.

Oncology Letters
|May 8, 2023
PubMed

Insights

Involucrasin A, a natural compound, effectively inhibits colorectal cancer (CRC) cell proliferation and induces apoptosis. It functions by modulating the Akt/MDM2/p53 pathway, showing promise for CRC treatment.

Area of Science:

  • Natural Products Chemistry
  • Cancer Biology
  • Molecular Pharmacology

Background:

  • Colorectal cancer (CRC) remains a leading cause of cancer mortality globally, with a persistent need for novel therapeutic agents.
  • Naturally derived compounds offer a promising avenue for discovering new antitumorigenic drugs.
  • The plant *Shuteria involucrata* (Wall.) Wight & Arn. is a potential source of bioactive molecules.

Purpose of the Study:

  • To evaluate the anticancer activity of the novel natural molecule Involucrasin A against HCT-116 colorectal cancer cells.
  • To elucidate the underlying molecular mechanisms of Involucrasin A's anti-CRC effects.
  • To assess the potential of Involucrasin A as a therapeutic candidate for colorectal cancer.

Main Methods:

  • Sulforhodamine B and colony formation assays were used to assess cell proliferation.
  • Flow cytometry and western blotting were employed to analyze apoptosis and protein expression.
  • Gene knockout and knockdown techniques were utilized to investigate the Akt/MDM2/p53 signaling pathway.

Main Results:

  • Involucrasin A demonstrated potent inhibition of HCT-116 CRC cell proliferation *in vitro*.
  • The compound induced apoptosis, evidenced by upregulated cleaved-caspase 6 and cleaved-caspase 9 levels.
  • Involucrasin A inhibited Akt and MDM2 phosphorylation, leading to increased p53 levels, a process dependent on the Akt/MDM2/p53 pathway.

Conclusions:

  • Involucrasin A exhibits significant antitumorigenic activities in HCT-116 CRC cells.
  • The mechanism involves the modulation of the Akt/MDM2/p53 signaling pathway.
  • Involucrasin A warrants further investigation in preclinical and clinical settings for CRC therapy.
Keywords:
Akt/murine double minute 2 homologue/p53 pathwayHCT-116 cellsShuteria involucrata (Wall.) Wight & Arncolorectal cancerinvolucrasin A

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