Cytoprotective and Antitumor Effects of Amifostine in Human Colon Cancer Cell Lines

Objectives: This study investigates the effects of amifostine on cell proliferation and apoptosis in HCT116 colorectal cancer cells, with a specific focus on the roles of p53 and c-Abl proteins.Methods: IC50 values were determined across various cell lines to assess drug sensitivity.The sensitivity of c-Abl+/+ and c-Abl-/-cells to amifostine was compared to evaluate the influence of c-Abl on drug response.Cell cycle progression was analyzed by assessing G2/M checkpoint arrest induced by amifostine.DNA damage was quantified by measuring r-H2AX accumulation.Apoptosis rates were determined, and the expression balance between Bcl-2 and Bax was analyzed to investigate their role in regulating cell survival and death.Results: c-Abl+/+ cells exhibited higher sensitivity to amifostine than c-Abl-/-cells.Interestingly, p53-deficient cell lines showed increased sensitivity to amifostine.Amifostine treatment induced G2/M checkpoint arrest, thereby inhibiting cell cycle progression in HCT116 cells.A significant accumulation of r-H2AX, a marker of DNA damage, was observed, with p53-deficient cells displaying higher levels of DNA damage.The presence of p53 significantly influenced apoptosis rates (P = 0.002), and the balance between Bcl-2 and Bax expression was critical in determining cell survival and death.Conclusion: Amifostine inhibits the proliferation of colorectal cancer cells through p53 signaling pathways.The study provides valuable insights into the role of p53 and c-Abl proteins in modulating the response to amifostine, suggesting that targeting these pathways could offer therapeutic potential for the treatment of colorectal cancer.