Related Experiment Video

Updated: Aug 9, 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

Inhibition of RelA phosphorylation sensitizes apoptosis in constitutive NF-kappaB-expressing and chemoresistant cells

S K Manna1, P Manna, A Sarkar

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

Cell Death and Differentiation
|April 29, 2006
PubMed

Insights

The compound P(3)-25 inhibits nuclear transcription factor kappaB (NF-kappaB) signaling, inducing apoptosis in breast cancer cells. This suggests P(3)-25 as a potential agent for combination chemotherapy.

Area of Science:

  • Medicinal Chemistry
  • Molecular Biology
  • Oncology

Background:

  • The compound 5-(4-methoxyarylimino)-2-N-(3,4-dichlorophenyl)-3-oxo-1,2,4-thiadiazolidine (P(3)-25) exhibits known antimicrobial and anesthetic properties.
  • Nuclear transcription factor kappaB (NF-kappaB) signaling is implicated in various cancers, including breast cancer.

Purpose of the Study:

  • To investigate the anti-tumorigenic activity of P(3)-25.
  • To elucidate the role of NF-kappaB in the anti-tumorigenic effects of P(3)-25.

Main Methods:

  • Assessed the effect of P(3)-25 on NF-kappaB-dependent reporter gene expression, adhesion molecules, and cyclooxygenase in constitutive NF-kappaB-expressing cells.
  • Investigated the impact of P(3)-25 on the phosphorylation of p65, the transcriptionally active subunit of NF-kappaB, and its upstream kinases.
  • Evaluated the ability of P(3)-25 to induce apoptosis in breast cancer cells, including doxorubicin-resistant lines, both alone and in combination with chemotherapeutic agents.

Main Results:

  • P(3)-25 inhibited NF-kappaB-dependent reporter gene expression, adhesion molecules, and cyclooxygenase.
  • P(3)-25 downregulated p65 phosphorylation by inhibiting upstream kinases (protein kinase A and casein kinase II) without affecting NF-kappaB DNA-binding activity.
  • P(3)-25 induced apoptosis in NF-kappaB-expressing and doxorubicin-resistant breast cancer cells and potentiated chemotherapy-induced apoptosis.

Conclusions:

  • P(3)-25 exerts anti-tumorigenic activity by inhibiting p65 phosphorylation via upstream kinases.
  • P(3)-25 enhances apoptosis induced by chemotherapeutic agents, suggesting its utility in combination chemotherapy.
  • These findings offer novel strategies for designing anticancer drugs for combination therapy.

More Related Videos

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity04:20

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity

Published on: February 9, 2024

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...