Selenium compounds activate early barriers of tumorigenesis

Area of Science:

• Oncology
• Cell Biology
• Biochemistry

Background:

• Selenium's role in cancer chemoprevention is primarily linked to apoptosis induction.
• The impact of selenium on early anti-tumorigenesis barriers like senescence and DNA damage response remains largely unexplored.

Purpose of the Study:

• To investigate whether selenium compounds can activate cellular senescence and DNA damage response in normal and cancerous cells.
• To elucidate the molecular mechanisms underlying selenium's effect on these early tumorigenesis barriers.

Main Methods:

• Normal and cancerous cells were treated with varying concentrations of sodium selenite, methylseleninic acid, and methylselenocysteine.
• Cellular senescence was assessed via senescence-associated beta-galactosidase expression and 5-bromo-2-deoxyuridine incorporation.
• DNA damage response activation, specifically the ataxia telangiectasia mutated (ATM) pathway, was analyzed. The role of reactive oxygen species was also investigated using antioxidants.

Main Results:

• Selenium compounds, at sub-lethal doses, induced cellular senescence in normal cells but not in cancer cells.
• The ataxia telangiectasia mutated (ATM) pathway was activated by selenium compounds, and its kinase activity was essential for the senescence response.
• Antioxidant pretreatment inhibited selenium-induced ATM activation and senescence, indicating a role for reactive oxygen species.

Conclusions:

• Selenium compounds activate early tumorigenesis barriers, specifically senescence, in non-cancerous cells through an ATM-dependent pathway.
• This selenium-induced senescence is mediated by reactive oxygen species and is specific to normal cells, suggesting a novel chemopreventive strategy.