In Vitro Anticancer Activity of the Light Stable Zinc Isotope (⁶⁴Zn) Compounds

Today, stable isotopes of zinc are actively used for diagnostic purposes in oncology. However, there is extremely limited data on the attempts to apply stable zinc isotopes in cancer therapy or about the molecular mechanisms of their effects on the biology of tumor cells. Therefore, in this in vitro research, we evaluated the cytotoxic activity of stable zinc isotope (⁶⁴Zn) enriched compounds against malignant cells and determined the mechanisms of their action.

Malignant and non-malignant cells of different histogenesis were used as objects of the study. The effect of the Zn⁶⁴aspartate, Zn⁶⁴glutamate, and Zn⁶⁴sulfate on cell viability in a comparative aspect was evaluated. Compounds containing ⁶⁴Zn stable isotope enriched to 99.2%. Western blot analysis was used to determine the expression level of apoptosis regulatory proteins.

Salts of ⁶⁴Zn with amino acids had the most significant cytotoxic effect on malignant cells. The studied tumor cells, and especially MB16 melanoma cells were the most sensitive to the cytotoxic effects of Zn⁶⁴aspartate. Zn⁶⁴aspartate showed more significant cytotoxic activity than Zn aspartate (with natural isotope distribution) in the studied cell models. Zn⁶⁴aspartate induced caspase-dependent cell death in A-549 cells and the p53-mediated apoptosis in melanoma cells.

Malignant cells were more sensitive to the cytotoxic effect of the Zn⁶⁴aspartate than normal cells. An increase in the intracellular concentration of ⁶⁴Zn, and hence isotope mass balance changes, may lead to the suppression of the viability and proliferation of malignant cells. These results can become the basis for developing a new generation of anticancer drugs.