Background: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, with increasing incidence in younger populations. Gamma radiation is a key therapeutic modality that induces DNA damage and activates the p53 pathway to promote apoptosis. However, the influence of p53 status on radiation response in CRC cells requires further clarification.
Materials and Methods: This narrative review synthesized data from PubMed, Scopus, and Web of Science up to May 2026, focusing on original studies examining gamma radiation-induced p53 pathway activation and apoptosis in CRC cells.
Results: In wild-type p53 cells (e.g. HCT116 p53+/+), gamma radiation stabilizes p53, leading to G1/S arrest and apoptosis through upregulation of pro-apoptotic genes (Bax, PUMA, NOXA) and downregulation of Bcl-2. In p53-mutant or -deficient cells (e.g. HCT116 p53−/−, HT-29), apoptosis occurs via p53-independent mechanisms including G2/M arrest, persistent DNA damage, and alternative signaling pathways (mitogen-activated protein kinase, phosphoinositide 3-kinase [PI3K]/protein kinase B), albeit with altered kinetics. Molecular evidence confirms Bax/Bcl-2 ratio shifts, caspase activation, and telomerase modulation. Major challenges include model variability, dose heterogeneity, and difficulties translating in vitro findings to clinical settings due to tumor resistance.
Conclusion: Gamma radiation effectively induces apoptosis in CRC cells through both p53-dependent and p53-independent routes. p53 status critically determines response mechanisms. These findings support personalized radiotherapy strategies that target both pathways to overcome resistance and improve therapeutic efficacy in CRC.