Folate deficiency induces a cell cycle-specific apoptosis in HepG2 cells

Area of Science:

• Cell Biology
• Biochemistry
• Cancer Research

Background:

• Folate metabolism and apoptosis are crucial in solid tissue-derived cells.
• HepG2 cells, a hepatoma model, offer insights into these processes.
• Limited investigation exists on folate's role in HepG2 cell apoptosis.

Purpose of the Study:

• To investigate the effects of folate deficiency on HepG2 cell metabolism and apoptosis.
• To elucidate the cell cycle mechanisms involved in folate-deficiency-induced apoptosis.
• To determine the role of p53 in this process.

Main Methods:

• Culturing HepG2 cells in folate-deficient media for 4 weeks.
• Assessing intracellular folate levels, cell viability, and DNA fragmentation.
• Analyzing cell cycle progression using flow cytometry and p53 expression via ELISA.

Main Results:

• Folate deficiency significantly reduced intracellular folate levels, induced growth arrest, and increased cell death.
• Apoptosis was confirmed by DNA fragmentation, chromatin condensation, and TUNEL assay.
• Cell cycle analysis revealed S-phase accumulation, G2/M block, and increased protein content, independent of p53.
• Folate supplementation normalized cell cycles and reduced DNA fragmentation.

Conclusions:

• HepG2 cells in folate-deficient medium exhibit reduced viability and increased apoptosis.
• Apoptosis is linked to cell cycle-specific mechanisms, not the p53 pathway.
• Folate is essential for maintaining HepG2 cell growth, viability, and normal cell cycle progression.