Impact of dietary ingredients on radioprotection and radiosensitization: a comprehensive review

Abstract

Radiation exposure poses significant health risks, particularly in radiotherapy and nuclear accidents. Certain dietary ingredients offer potential radioprotection and radiosensitization. In this review, we explore the impact of dietary ingredients, including vitamins, minerals, antioxidants, and other bioactive compounds, on radiation sensitivity and their potential for radioprotection. Radiosensitizers reoxygenate hypoxic tumor cells, increase the radiolysis of water molecules, and regulate various molecular mechanisms to induce cytotoxicity and inhibit DNA repair in irradiated tumor cells. Several dietary ingredients, such as vitamins C, E, selenium, and phytochemicals, show promise in protecting against radiation by reducing radiation-induced oxidative stress, inflammation, and DNA damage. Radioprotectors, such as ascorbic acid, curcumin, resveratrol, and genistein, activate and modulate various signaling pathways, including Keap1-Nrf2, NF-κB, PI3K/Akt/mammalian target of rapamycin (mTOR), STAT3, and mitogen-activated protein kinase (MAPK), in response to radiation-induced oxidative stress, regulating inflammatory cytokine expression, and promoting DNA damage repair and cell survival. Conversely, natural dietary radiosensitizers impede these pathways by enhancing DNA damage and inducing apoptosis in irradiated tumor cells. Understanding the molecular basis of these effects may aid in the development of effective strategies for radioprotection and radiosensitization in cancer treatment. Dietary interventions have the potential to enhance the efficacy of radiation therapy and minimize the side effects associated with radiation exposure.

Keywords: Dietary ingredients; apoptosis; cell survival; radioprotector; radiosensitivity; radiosensitizer.

Figure 1.

Flow chart of the selection of studies included in the review.

Figure 2.

Dietary ingredients with radioprotective and radiosensitizing activities.

Figure 3.

Stress response pathways modulated by radioprotecting and radiosensitizing dietary ingredients. When exposed to IR, free radicals such as ROS are produced in the cellular system. Radiosensitizers enhance radiation-induced ROS production to break DNA double strands, induce p53-mediated apoptosis, and arrest the cell cycle in tumor cells. Radiosensitizers can also facilitate the p53-independent or oxidative stress-mediated mitochondrial cytochrome C pathway in tumor cells to promote apoptosis. Furthermore, radiosensitizers sensitize tumor cells to radiation by inhibiting the MAPK, STAT3, PI3K/Akt/mTOR, NF-κB, and Nrf2 pathways, leading to transcription of various genes involved in cell proliferation, cell survival, DNA damage repair, and antioxidation. On the other hand, radioprotective dietary ingredients activate the MAPK, STAT3, PI3K/Akt/mTOR, NF-κB, and Nrf2 pathways to minimize the detrimental effects of ROS on normal cells. Additionally, radioprotectors inhibit p53-dependent and p53-independent apoptosis in response to oxidative stress, thereby protecting normal cells from the damaging effects of radiation.