Biomedical Science Letters (대한의생명과학회지)

The Korean Society for Biomedical Laboratory Sciences (대한의생명과학회)
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Cytoprotective and Antitumor Effects of Amifostine in Human Colon Cancer Cell Lines

  • Received : 2024.10.04
  • Accepted : 2024.11.26
  • Published : 2024.12.31
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Abstract

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.

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References

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