The influence of apigenin on cellular responses to radiation: From protection to sensitization

Abstract Apigenin, a dietary flavonoid, has gained increasing attention for its potential therapeutic applications in radiation protection and radiosensitization. Ionizing radiation (IR) can harm healthy cells, but as radiotherapy remains crucial in cancer treatment. Owing to the remarkable application of radiotherapy in the treatment of cancers, it is vital to protect healthy cells from radiation hazards while increasing the sensitivity of cancer cells to radiation. This article reviews the current understanding of apigenin's radioprotective and radiosensitive properties with a focuses on the involved signaling pathways and key molecular targets. When exposed to irradiation, apigenin reduces inflammation via cyclooxygenase‐2 inhibition and modulates proapoptotic and antiapoptotic biomarkers. Apigenin's radical scavenging abilities and antioxidant enhancement mitigate oxidative DNA damage. It inhibits radiation‐induced mammalian target of rapamycin activation, vascular endothelial growth factor (VEGF), matrix metalloproteinase‐2 (MMP), and STAT3 expression, while promoting AMPK, autophagy, and apoptosis, suggesting potential in cancer prevention. As a radiosensitizer, apigenin inhibits tumor growth by inducing apoptosis, suppressing VEGF‐C, tumor necrosis factor alpha, and STAT3, reducing MMP‐2/9 activity, and inhibiting cancer cell glucose uptake. Cellular and animal studies support apigenin's radioprotective and anticancer potential, making it a potential candidate for further research. Investigation into apigenin's therapeutic efficacy in diverse cancer types and radiation damage is essential.