Differential Effects of Confinement-Induced ROS Accumulation on Highly Motile Cancerous and Non-Cancerous Cells

Area of Science:

• Cell biology
• Biophysics
• Cancer research

Background:

• Cells in vivo encounter spatial constraints, causing deformation and potential DNA damage.
• DNA damage from confinement is linked to increased reactive oxygen species (ROS).

Purpose of the Study:

• To investigate the impact of oxidative stress on cell behavior under spatial confinement.
• To explore the role of ROS in confinement-induced cellular responses and migration.

Main Methods:

• Utilized microchannel devices to control cell confinement degree and duration.
• Measured ROS levels in HT-1080 fibrosarcoma cells and human dermal fibroblasts.
• Assessed the effects of N-Acetyl-L-cysteine (NAC) antioxidant treatment on cellular responses.

Main Results:

• Confinement significantly increased ROS levels in both cancer and normal cells.
• NAC treatment reduced ROS, suppressed p53 activation, and enhanced cell survival.
• NAC preferentially reduced dorsal perinuclear actin fibers in confined cancer cells, correlating with reduced nuclear rupture and increased migration.

Conclusions:

• Oxidative stress plays a differential role in the response of cancerous versus non-cancerous cells to confinement.
• Antioxidant interventions may inadvertently support tumor progression by enhancing cancer cell migration.