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Updated: Jun 26, 2026
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
Summary
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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