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Updated: Jun 26, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Decrease in RelA phosphorylation by inhibiting protein kinase A induces cell death in NF-kappaB-expressing and

Sunil K Manna1, Charitha Gangadharan

  • 1Laboratory of Immunology, Centre for DNA Fingerprinting & Diagnostics, Nacharam, Hyderabad 500076, India. manna@cdfd.org.in

Molecular Immunology
|January 9, 2009
PubMed

Insights

A novel compound, P(3)-25, induces cell death in drug-resistant cancer cells by inhibiting protein kinase A (PKA) and nuclear factor-kappa B (NF-kappaB) activity. This mechanism offers potential for new cancer therapies.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Pharmacology

Background:

  • Nuclear factor-kappa B (NF-kappaB) signaling, involving the RelA (p65) subunit, drives inflammation and tumorigenesis.
  • NF-kappaB activation is a key target for cancer therapy, particularly in doxorubicin-resistant cells.

Purpose of the Study:

  • To investigate the effect of P(3)-25, a dichlorophenyl derivative of 1,2,4-thiadiazolidine, on NF-kappaB-expressing and doxorubicin-resistant cells.
  • To elucidate the molecular mechanism underlying P(3)-25-induced cell death.

Main Methods:

  • Assessed cell death induction in NF-kappaB-expressing and doxorubicin-resistant cell lines.
  • Measured NF-kappaB DNA binding activity and expression of NF-kappaB-dependent genes.
  • Investigated the effect of P(3)-25 on protein kinase A (PKA) activity and p65 phosphorylation.
  • Evaluated P(3)-25's ability to potentiate chemotherapeutic agents.

Main Results:

  • P(3)-25 induced significant cell death in NF-kappaB-expressing and doxorubicin-resistant cells.
  • P(3)-25 partially inhibited NF-kappaB DNA binding but completely suppressed NF-kappaB-dependent gene expression.
  • P(3)-25 directly inhibited PKA catalytic activity, leading to decreased p65 phosphorylation and NF-kappaB transcriptional activity.
  • P(3)-25 enhanced the efficacy of other chemotherapeutic drugs.

Conclusions:

  • P(3)-25 induces apoptosis in resistant cancer cells by inhibiting PKA and subsequently suppressing the NF-kappaB pathway.
  • This targeted inhibition of PKA and NF-kappaB signaling by P(3)-25 presents a promising strategy for developing novel chemotherapeutic agents for tumor therapy.

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