Anti-Cancer Effects of Soy Isoflavones against Cancer by Radiosensitizing Properties: A Systematic Review

Abstract

Background: It is necessary to investigate the targets and pathways on which soy isoflavones act as radiosensitizers for their future use and their potential therapeutic effects. Objective: This systematic review aims to discuss and highlight future perspectives on the radiosensitizing effects of soy isoflavones against cancer cells. Methods: We thoroughly searched multiple databases, such as PubMed/MEDLINE, Cochrane Library, Web of Science, and Scopus. We aimed to find studies investigating the effectiveness of soy isoflavones in increasing the sensitivity of different types of cancer to radiation treatment. We extracted data according to the study's aim, and the studies' outcomes were reviewed. Results: The radiosensitizing effects of soy isoflavones are related to the accumulation of intracellular Reactive Oxygen Species (ROS), reducing Glutathione (GSH), Nuclear factor erythroid 2–related factor 2 (Nrf2) and Heme Oxygenase-1 (HO-1). They also induce cancer cell apoptosis through inhibited Nuclear factor kappa B (NF-κB), apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) and HIF-1α, upregulation of poly (ADP-ribose) polymerases (PARP) and improve cytochrome c, upregulation Bcl-2-associated X protein (Bax), inhibited B-cell lymphoma-extra-large (Bcl-xL) and activation of caspase-3 and -8. Moreover, by inhibiting p21, increased phosphorylation of p53 and PARP-1-dependent ATP depletion caused DNA damage and impaired DNA repair. Soy isoflavones also arrest the cell cycle by interfering with the G2/M checkpoint. Conclusion: In vivo and in vitro studies indicated that soy isoflavones enhanced radiotherapy effects on cancer cells with protective effects on healthy cells. Also, clinical studies reported safe and satisfactory properties of soy isoflavones along with radiotherapy in cancer treatment. © 2025 Bentham Science Publishers.