Anticancer potential of radioactively activated zinc: mechanisms and therapeutic applications

Zinc (Zn), an essential trace element, has been shown to exhibit antiproliferative effects at high concentrations and to serve various functions in human health. Numerous studies have been undertaken to enhance the efficacy of zinc. In this study, the therapeutic efficacy of zinc in terms of activation by ionizing radiation was investigated, and whether this would increase its efficacy was determined. In this study, Zn-65 was detected by exposing zinc to X-rays using a novel approach. The present study investigates the biological effects of low-dose gamma irradiation with Zn-65 compared with zinc alone on MCF-7 breast cancer cells. Human umbilical cord endothelial cells (HUVECs) were used as a standard cell control. The study investigated the biological effects of Zn-65 (IR-Zn) on MCF-7 breast cancer cells, comparing them with non-irradiated zinc, using human umbilical cord endothelial cells (HUVECs) as a control. Cytotoxic activity, cell proliferation, apoptosis, cell cycle progression, and drug resistance profiles were evaluated. Our findings show that IR-Zn significantly enhances anticancer activity by inducing premature cell cycle arrest at the G0/G1 phase, promoting apoptosis, and suppressing ABCG2-mediated drug resistance mechanisms. This is the first study to demonstrate that low doses of gamma-emitting Zn-65 can elicit potent, selective cytotoxicity against cancer cells without severely damaging normal cells. The findings indicate that weak gamma-emitting Zn-65 may be a viable targeted and low-toxicity radiopharmaceutical candidate for prospective oncological applications. © The Author(s) 2026.