Related Experiment Video
Updated: May 15, 2026
07:40
A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions
Published on: May 27, 2021
Different cell cycle modulation by celecoxib at different concentrations
1Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Cancer Biotherapy & Radiopharmaceuticals
|December 28, 2012
Summary
Celecoxib, a cyclooxygenase (COX)-2 inhibitor, alters cancer cell cycles differently based on concentration. Low doses cause G1 arrest, high doses cause G2/M arrest, impacting radiotherapy effectiveness.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Cyclooxygenase (COX)-2 inhibitors exhibit varied effects on cell cycle regulation.
- The concentration-dependent impact of these inhibitors on cell cycle modulation remains incompletely understood.
- Cancer cells often exhibit altered COX-2 expression, influencing therapeutic responses.
Purpose of the Study:
- To investigate the concentration-dependent effects of celecoxib, a selective COX-2 inhibitor, on cell cycle regulation.
- To determine how celecoxib influences cell cycle progression in irradiated cancer cells with varying COX-2 expression levels.
- To elucidate the molecular mechanisms underlying celecoxib's effects on cell cycle checkpoints and apoptosis.
Main Methods:
- Utilized four cancer cell lines with stable COX-2 knockdown or overexpression.
- Treated cell lines with various concentrations of celecoxib, with or without radiation.
- Analyzed cell cycle distribution, apoptosis, and expression of key regulatory proteins (Cdc25C, p21).
Main Results:
- Celecoxib induced G1 arrest at lower concentrations and G2/M arrest at higher concentrations, irrespective of COX-2 levels.
- Radiation-induced G2/M arrest was potentiated by low celecoxib concentrations but attenuated by high concentrations.
- Celecoxib activated Cdc25C and inhibited p21, leading to G2 checkpoint deactivation and secondary apoptosis in irradiated cells, dependent on COX-2.
Conclusions:
- Celecoxib exhibits distinct concentration-dependent effects on cancer cell cycle progression.
- The drug modulates the G2 checkpoint via Cdc25C and p21 pathways, influencing radiosensitivity.
- These findings suggest potential clinical applications of celecoxib in combination with radiotherapy for cancer treatment.
Related Concept Videos
02:34Inhibition 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...
02:34Inhibition 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...
02:11The Cell Cycle Control System
The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...
01:28The Cell Cycle Control System
The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
01:27Molecular Factors Affecting Cell Division
Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
02:39Positive Regulator Molecules
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.