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PI-103 attenuates PI3K-AKT signaling and induces apoptosis in murineT-cell lymphoma

Akhilendra Kumar Maurya1, Manjula Vinayak1

  • 1a Biochemistry & Molecular Biology Laboratory, Department of Zoology, Institute of Science , Banaras Hindu University , Varanasi , India.

Leukemia & Lymphoma
|September 24, 2016
PubMed

Insights

PI-103, a specific inhibitor of PI3K-p110α, demonstrated anti-cancer effects against murine T-cell lymphoma. It reduced cancer cell proliferation and induced apoptosis by attenuating the PI3K-AKT signaling pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Aberrant activation of the phosphoinositide 3-kinase-AKT (PI3K-AKT) signaling pathway is implicated in various cancers.
  • Targeting specific PI3K isoforms offers a therapeutic advantage over broad-spectrum inhibitors.
  • PI-103 is a selective inhibitor of the p110α isoform of class I PI3K.

Purpose of the Study:

  • To investigate the anti-carcinogenic potential of PI-103 in Dalton's lymphoma ascites (DLA) cells.
  • To elucidate the mechanism by which PI-103 affects cancer cell signaling and viability.
  • To assess the impact of PI-103 on apoptosis and reactive oxygen species (ROS) in lymphoma cells.

Main Methods:

  • Treatment of DLA cells with PI-103.
  • Assessment of cell proliferation and apoptosis using Annexin V binding, nuclear fragmentation, and active caspase 3 assays.
  • Analysis of PI3K-AKT signaling pathway components (p110α, phospho-p85α, phospho-AKT, PKCα) via Western blotting.
  • Evaluation of ROS levels in hydrogen peroxide (H₂O₂)-induced DLA cells.

Main Results:

  • PI-103 significantly inhibited DLA cell proliferation and induced apoptosis.
  • PI-103 treatment led to the downregulation of key signaling molecules including p110α, phospho-p85α, phospho-AKT, and PKCα.
  • ROS accumulation was reduced in H₂O₂-induced DLA cells treated with PI-103.
  • The observed effects were consistent in both standard DLA cells and H₂O₂-induced DLA cells.

Conclusions:

  • PI-103 effectively attenuates the PI3K-AKT signaling pathway in murine T-cell lymphoma.
  • PI-103 exerts anti-carcinogenic effects through the induction of apoptosis.
  • Targeting PI3K-p110α with PI-103 represents a potential therapeutic strategy for T-cell lymphoma.
Keywords:
PI-103PI3K-AKT signalingapoptosislymphoma

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