Radiosensitizing effect of astaxanthin on radiation-induced cytotoxicity in breast cancer cells

BACKGROUND: Radiotherapy (RT) is a primary treatment for cancer, including breast cancer, but its effectiveness is limited by severe side effects. Radiosensitization using natural products can enhance efficacy while reducing radiation doses. Astaxanthin (AST), a natural carotenoid with antioxidant properties, requires further investigation for its role in cancer therapy. Especially in many previous studies, AST found to has prooxidant effect in cancer cells reverse its antioxidant effect in normal cells. METHODS: This study explored AST’s potential to enhance the cytotoxic effects of ionizing radiation (IRR) against MCF7 breast cancer cells and the underlying mechanisms. Cytotoxicity, apoptosis induction, anti-metastatic activity, and cell cycle distribution were analyzed in response to IRR with and without AST. RESULTS: IRR alone showed limited cytotoxicity, whereas addition of AST significantly enhanced IRR’s effects, reducing IC50 by ten folds in combination treatment. AST increased apoptosis markers (caspase-3 and BAX/BCL2 ratio) by 16% and 67.8%, respectively. It also decreased proliferation index and S-phase ratio by 43.24% and 42.6%, respectively. AST further reduced metastatic markers MMP2 and MMP9 by 25% and 33.8%, respectively, in combination therapy. Additionally, AST exhibited a pro-oxidant effect, elevating MDA and H₂O₂ levels by 16.9% and 18.9%, respectively. It also caused cell cycle arrest at the S and G2/M phases, making cells more susceptible to IRR. CONCLUSION: These findings confirm AST’s radiosensitizing effect via apoptosis induction, cell cycle disruption, and anti-metastatic activity, supporting its potential in enhancing radiotherapy efficacy for breast cancer cells. Further research is warranted to explore its application in cancer treatment.