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Apigetrin inhibits gastric cancer progression through inducing apoptosis and regulating ROS-modulated STAT3/JAK2

Qian Sun1, Na-Na Lu2, Lei Feng3

  • 1Pharmacy Intravenous Admixture Service Centre, Affiliated Hospital of Jining Medical University, Jining 272029, China.

Biochemical and Biophysical Research Communications
|February 7, 2018
PubMed

Insights

Apigetrin (APG), a flavonoid, suppresses human gastric cancer by inducing apoptosis and inhibiting key signaling pathways like STAT3/JAK2. It generates reactive oxygen species (ROS) to achieve these anti-cancer effects.

Area of Science:

  • Molecular Biology
  • Oncology
  • Natural Product Chemistry

Background:

  • Flavonoids exhibit diverse bioactivities, including potential anti-cancer properties.
  • Apigetrin (APG) is a flavonoid with known cellular effects, but its mechanism against gastric cancer is unclear.

Purpose of the Study:

  • To investigate the anti-cancer effects and underlying mechanisms of Apigetrin (APG) in human gastric cancer cells.
  • To explore APG's role in apoptosis induction, reactive oxygen species (ROS) generation, and key signaling pathways.

Main Methods:

  • In vitro studies on human gastric cancer cells treated with APG.
  • Analysis of apoptosis-related proteins (Bcl-2, Bax, Caspase-9/-3, PARP) and ROS levels.
  • Investigation of STAT3, JAK2, and Src signaling pathways, including the effect of ROS scavenger N-acetyl-cysteine (NAC).
  • In vivo xenograft mouse models to assess APG's anti-tumor efficacy.

Main Results:

  • APG suppressed gastric cancer cell proliferation and induced apoptosis by modulating Bcl-2, Bax, and caspase cleavage.
  • APG treatment increased intracellular ROS generation, which was crucial for APG-induced apoptosis.
  • APG inhibited constitutive and IL-6-stimulated STAT3, JAK2, and Src activation, a process partially dependent on ROS.
  • APG administration significantly inhibited tumor growth in vivo by inducing apoptosis and suppressing the STAT3/JAK2 pathway.

Conclusions:

  • Apigetrin (APG) exhibits significant anti-cancer effects against human gastric cancer through apoptosis induction and STAT3/JAK2 pathway inhibition.
  • ROS generation plays a critical role in mediating APG's pro-apoptotic and anti-proliferative effects.
  • APG demonstrates potential as a therapeutic candidate for human gastric cancer treatment.
Keywords:
ApigetrinApoptosisGastric cancerROSSTAT3/JAK2

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