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Cytoprotective and Antitumor Effects of Amifostine in Human Colon Cancer Cell Lines
Biomed Sci Letters 2024;30:276-283
Published online December 31, 2024;  https://doi.org/10.15616/BSL.2024.30.4.276
© 2024 The Korean Society For Biomedical Laboratory Sciences.

Younglag Cho1,* and Eun Ju Lee2,†,*

1LigaChemBio, Daejeon 34002, Korea
2Department of Clinical Laboratory Science, Daejeon Health University, Daejeon 34504, Korea
Correspondence to: †Eun Ju Lee
Department of Clinical Laboratory Science, Daejeon Health University, 21 Chungjeong St., Dong-gu, Daejeon 34504, Korea
Tel: +82-42-670-9163, Fax: +82-42-670-9160
E-mail: e16lee@hit.ac.kr
ORCID: https://orcid.org/0009-0004-2956-4798

*Professor.
Received October 4, 2024; Revised November 18, 2024; Accepted November 26, 2024.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 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.
Keywords : Amifostine, HCT116 cell lines, c-Abl, p53, p21, Cell cycle, Apoptosis