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Updated: Jul 13, 2026
11:23
Measuring Cell Cycle Progression Kinetics with Metabolic Labeling and Flow Cytometry
Published on: May 22, 2012
Regulation of normal cell cycle progression by flavin-containing oxidases
P Venkatachalam1, S M de Toledo, B N Pandey
1Department of Radiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ, USA.
Oncogene
|July 20, 2007
Summary
Reactive oxygen species (ROS) generated by NAD(P)H oxidase regulate cell cycle progression. Inhibiting this enzyme causes a G1 cell cycle delay, suggesting it
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- Reactive oxygen species (ROS) play crucial roles in cellular signaling.
- Flavin-containing oxidases, like NAD(P)H oxidase, are key sources of cellular ROS.
- Cell cycle regulation is vital for normal proliferation and preventing diseases like cancer.
Purpose of the Study:
- To investigate the mechanisms by which ROS from flavin-containing oxidases regulate cell cycle progression.
- To determine the role of NAD(P)H oxidase-derived ROS in controlling cell cycle checkpoints.
- To explore the potential of targeting NAD(P)H oxidase for cancer therapy.
Main Methods:
- Human and rodent fibroblasts were treated with diphenyleneiodonium (DPI), a flavoprotein inhibitor.
- NAD(P)H oxidase activity, ROS levels, protein degradation, and cell cycle progression (G1, G2 phases) were measured.
- Signaling pathways involving p53, p21(Waf1), ATM, and mitogen-activated kinases were analyzed.
- ROS generators (gamma-radiation, t-butyl-hydroperoxide) were used to modulate ROS levels.
Main Results:
- DPI treatment reduced NAD(P)H oxidase activity and ROS, leading to increased proteolysis of cell cycle regulators (cyclin D1, p21(Waf1)).
- Inhibition of NAD(P)H oxidase induced a significant G1 cell cycle delay, dependent on ATM, PHOX91, and WAF1, with partial dependence on p53.
- Restoring ROS levels attenuated the G1 delay, while nitric oxide synthase inhibition did not affect G1 to S progression.
- DPI also caused an attenuated G2 delay in proliferating cells.
Conclusions:
- Nonphagocytic NAD(P)H oxidase activity is critical for regulating normal cellular proliferation via ROS production.
- ATM signaling is a key mediator in the G1 checkpoint control influenced by NAD(P)H oxidase.
- NAD(P)H oxidase represents a potential therapeutic target for arresting cancer cell proliferation in the G1 phase.
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