Inositol Hexaphosphate Inhibits Proliferation and Induces Apoptosis of Colon Cancer Cells by Suppressing the AKT/mTOR

Małgorzata Kapral1, Joanna Wawszczyk2, Katarzyna Jesse3

  • 1Department of Biochemistry, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jedności 8, 41-200 Sosnowiec, Poland. mkapral@sum.edu.pl.

Insights

Inositol hexaphosphate (InsP6) inhibits colon cancer cell growth and promotes apoptosis by targeting the AKT/mTOR pathway. This natural compound modulates key gene and protein expressions, offering a potential therapeutic strategy for colon cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The AKT/mammalian target of rapamycin (mTOR) signaling pathway is crucial for colon cancer cell proliferation and survival.
  • Inositol hexaphosphate (InsP6), a natural phytochemical, shows anticancer potential, but its mechanisms in colon cancer are not fully elucidated.
  • Targeting the AKT/mTOR pathway is a promising strategy for colon cancer therapy.

Purpose of the Study:

  • To investigate the in vitro anticancer effects of InsP6 on colon cancer cells.
  • To determine InsP6's impact on cell proliferation and apoptosis.
  • To elucidate the molecular mechanisms involving the inhibition of AKT1 kinase and p70S6K1 (mTOR effector) by InsP6.

Main Methods:

  • Colon cancer Caco-2 cells were treated with varying concentrations of InsP6 (1 mM, 2.5 mM, 5 mM).
  • Cell proliferation was assessed using 5-bromo-2'-deoxyuridine (BrdU) incorporation.
  • Cell cycle, apoptosis, gene expression (RT-qPCR), protein levels (ELISA), and kinase activity assays were performed.

Main Results:

  • InsP6 significantly inhibited colon cancer cell proliferation and induced apoptosis.
  • InsP6 increased the expression of p21, p27, caspase 3, and caspase 9.
  • InsP6 decreased AKT1 and S6K1 mRNA levels and suppressed AKT1 and p70S6K1 phosphorylation, indicating AKT/mTOR pathway inhibition.

Conclusions:

  • InsP6 exhibits anticancer activity against colon cancer cells by inhibiting the AKT/mTOR pathway.
  • InsP6 reduces proliferation and induces apoptosis through modulation of key pathway components.
  • InsP6 represents a potential therapeutic agent for colon cancer, warranting further investigation.

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