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

Abstract

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.