Related Experiment Video

Updated: Jun 14, 2025

Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells
13:38

Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells

Published on: January 18, 2017

12.2K

Novel Celecoxib Derivative, RF26, Blocks Colon Cancer Cell Growth by Inhibiting PDE5, Activating cGMP/PKG Signaling,

Sara Sigler1, Mohammad Abdel-Halim2, Reem K Fathalla2

  • 1Department of Pharmacology, Drug Discovery Research Center, Mitchell Cancer Institute, University of South Alabama, Mobile, AL, 36608, USA.

Anti-Cancer Agents in Medicinal Chemistry
|September 3, 2024
PubMed
Abstract

Insights

A novel PDE5 inhibitor, RF26, shows potent anticancer activity against colorectal cancer (CRC) cells by suppressing growth and inducing apoptosis. PDE5 is crucial for CRC tumor growth, making it a promising therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Phosphodiesterase type 5 (PDE5) is overexpressed in colorectal cancer (CRC) and drives cancer cell proliferation.
  • PDE5 inhibitors, like sildenafil, have demonstrated cancer chemopreventive potential.
  • Novel PDE5 inhibitors are being investigated for their anticancer efficacy.

Purpose of the Study:

  • To determine the anticancer activity of a novel PDE5 inhibitor, RF26, in colorectal cancer (CRC) cells.
  • To investigate the role of PDE5 in colorectal cancer (CRC) tumor growth *in vivo*.
  • To characterize RF26's mechanism of action, including its effects on cell signaling pathways.

Main Methods:

  • Human CRC cell lines were used to assess RF26's anticancer effects.
  • Measurements included cell growth, cGMP-dependent protein kinase (PKG) activity, β-catenin levels, TCF/LEF transcriptional activity, cell cycle distribution, and apoptosis.
  • CRISPR/cas9 PDE5 knockout techniques were employed to validate PDE5's role in RF26's activity and as a cancer target.

Main Results:

  • RF26 demonstrated superior potency in suppressing CRC cell growth compared to celecoxib and sildenafil.
  • RF26 activated PKG signaling, reduced β-catenin levels, inhibited TCF/LEF activity, induced G1 cell cycle arrest, and promoted apoptosis.
  • PDE5 knockout CRC cells showed decreased sensitivity to RF26, slower proliferation, and impaired tumor formation in mice.

Conclusions:

  • RF26 exhibits significant anticancer activity against colorectal cancer (CRC).
  • PDE5 plays a critical role in colorectal cancer (CRC) tumorigenesis.
  • Further research into RF26 for cancer prevention and treatment is warranted.
Keywords:
PDE5PKGcGMPcelecoxibcolorectal cancerpyrazolines.β-catenin

More Related Videos

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies09:29

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

13.7K
A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions07:40

A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions

Published on: May 27, 2021

4.1K

Related Concept Videos

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...
4.7K
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...
7.4K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.5K
Drugs for Treatment of Ulcerative Colitis in IBD01:29

Drugs for Treatment of Ulcerative Colitis in IBD

Ulcerative colitis is a chronic inflammatory condition primarily affecting the colon and rectum. The primary drugs used in the treatment of ulcerative colitis are aminosalicylates. They exhibit anti-inflammatory and immunosuppressive properties. They modulate inflammatory mediators and inhibit the activity of nuclear factor κB (NF-κB). Aminosalicylates also reduce inflammation by inhibiting prostaglandin and leukotriene production and decreasing neutrophil chemotaxis and superoxide...
130