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PI-103 and Quercetin Attenuate PI3K-AKT Signaling Pathway in T- Cell Lymphoma Exposed to Hydrogen Peroxide

Akhilendra Kumar Maurya1, Manjula Vinayak1

  • 1Biochemistry & Molecular Biology Laboratory, Centre for Advanced Study in Zoology, Institute of Science, Banaras Hindu University, Varanasi-221005, India.

Plos One
|August 6, 2016
PubMed

Insights

Hydrogen peroxide (H2O2) increases oxidative stress and activates the PI3K-AKT pathway in lymphoma cells. The flavonoid quercetin and PI3K inhibitor PI-103 both reduce ROS and suppress this pathway, suggesting similar mechanisms of action.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The Phosphatidylinositol 3 kinase-protein kinase B (PI3K-AKT) pathway is frequently activated in cancer, making it a key drug target.
  • Reactive oxygen species (ROS), such as hydrogen peroxide (H2O2), are linked to oxidative stress and tumor microenvironment adaptation.
  • Quercetin, a dietary flavonoid, is recognized for its potential health benefits and antioxidant properties.

Purpose of the Study:

  • To investigate the PI3K-AKT signaling pathway in H2O2-exposed Dalton's lymphoma ascites (DLA) cells.
  • To analyze the regulatory effects of quercetin and the PI3K inhibitor PI-103 on the PI3K-AKT pathway in this model.
  • To understand the role of oxidative stress in modulating key components of the PI3K-AKT pathway.

Main Methods:

  • DLA cells were exposed to 1mM H2O2 for 30 minutes to induce oxidative stress.
  • Levels of ROS, phosphorylation of PI3K, PDK1, AKT (Ser-473 and Thr-308), BAD, ERK1/2, TNFR1, and PTEN were analyzed.
  • The effects of quercetin and PI-103 on these markers in H2O2-treated cells were evaluated.

Main Results:

  • H2O2 exposure led to increased ROS accumulation, enhanced phosphorylation of PI3K, PDK1, AKT, BAD, ERK1/2, and TNFR1, and decreased PTEN levels.
  • Both quercetin and PI-103 effectively suppressed elevated ROS levels.
  • Both agents significantly down-regulated H2O2-induced phosphorylation of AKT, PDK1, and BAD, reduced TNFR1 levels, and increased PTEN levels.

Conclusions:

  • Quercetin and PI-103 exhibit similar mechanisms in attenuating the PI3K-AKT pathway in H2O2-induced lymphoma cells.
  • These findings highlight the potential of quercetin as a modulator of cancer-related signaling pathways involved in oxidative stress.
  • Targeting the PI3K-AKT pathway with agents like quercetin may offer therapeutic strategies for cancers associated with oxidative stress.

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