Copper-nitrite complexes release nitric oxide and selectively induce oral precancer and cancer cell apoptosis.

Nitric oxide (NO) is a small, short-lived gas molecule that influences various critical functions in living organisms. It involves multiple physiological processes, including cardiovascular function, metabolism, neurotransmission, immunity, and aberrant NO signaling leads to various disorders such as cardiovascular diseases, diabetes, and cancers. In this study, we explored the potential application of copper-nitrite complexes in treating oral precancer and cancer. The copper-nitrite complexes, L1Cu(NO2) and L2Cu(NO2), were shown to release NO into cells and selectively induce cytotoxicity to oral precancer and cancer cells. Notably, L1Cu(NO2) inhibited oral cancer cell proliferation by causing G0/G1 phase cell cycle arrest. Furthermore, L1Cu(NO2) induced cell apoptosis and upregulated the expression of p-PRAS40 (proline-rich Akt substrate of 40 kDa) in oral cancer cells. All these results reveal the therapeutic potential of copper-nitrite complexes, especially L1Cu(NO2), to be developed as a targeted therapy against oral precancer and cancer.