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Hesperetin regulates PI3K/Akt and mTOR pathways to exhibit its antiproliferative effect against colon cancer cells

Gowrikumar Saiprasad1, Palanivel Chitra1, Ramar Manikandan2

  • 1Department of Biochemistry, Cell Biology Laboratory, University of Madras, Chennai, India.

Biotechnic & Histochemistry : Official Publication of the Biological Stain Commission
|August 22, 2024
PubMed

Insights

Hesperetin, a citrus flavonoid, effectively inhibits colon cancer cell growth by inducing apoptosis and autophagy. It regulates the Akt and mTOR signaling pathways, showing therapeutic potential against colon carcinoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Hesperetin, a citrus flavonoid, is recognized for its anticancer properties, yet its precise mechanisms against colon cancer remain unclear.
  • Understanding hesperetin's molecular targets is crucial for developing effective colon cancer therapies.

Purpose of the Study:

  • To elucidate the anticancer mechanisms of hesperetin in colon cancer cells.
  • To investigate hesperetin's effects on cell proliferation, apoptosis, and autophagy.
  • To analyze the involvement of the PI3K/Akt/mTOR signaling pathway.

Main Methods:

  • HCT-15 colon cancer cells were treated with varying concentrations of hesperetin.
  • Immunoblotting was employed to assess protein expression and phosphorylation.
  • Scanning and transmission electron microscopy were used to examine cellular changes.

Main Results:

  • Hesperetin significantly reduced colon cancer cell proliferation and viability in a dose- and time-dependent manner.
  • Apoptosis was induced via a caspase-dependent pathway.
  • Hesperetin inhibited Akt phosphorylation and increased PTEN, suppressing the PI3K/Akt axis.
  • Autophagy was enhanced by hesperetin through mTOR dephosphorylation, upregulating Beclin-1 and LC3-II.
  • Hesperetin potentiated the effects of Akt and mTOR inhibitors.

Conclusions:

  • Hesperetin exhibits anticancer effects by inducing apoptosis and enhancing autophagy in colon cancer cells.
  • The therapeutic efficacy of hesperetin involves the regulation of the Akt and mTOR signaling pathways.
  • Hesperetin demonstrates significant potential as a therapeutic agent for colon carcinoma.
Keywords:
Autophagycolon cancerflavonoidhesperetinmTOR apoptosis

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