Anti-tumor effects of valproate zinc complexes on a lung cancer cell line

Abstract Lung cancer is one of the most common types of cancer worldwide and the development of new treatment strategies is needed. Valproate exhibits anti-cancer properties and has been studied as a candidate for cancer therapy. Novel treatments with synthesized coordination complexes with valproate bioisosteres are promising, as they are often more effective and selective than organic molecules. We evaluated the anti-tumoral effects of two ternary complexes containing Zn+2, valproate, and 2,2′-bipyridine (complex 1) or nicotinamide (complex 2) in a lung cancer cell line. Both complexes 1 and 2 exerted a 50% reduction in the viability of human epithelial lung cells (A549), indicating that coordination with Zn+2 improves the cytotoxic effects of valproate. Complex 1 increased the frequency of apoptotic cells 6-fold compared to vehicle, but it was less selective to tumor cells than complex 2. Complex 2 reduced the frequency of cells in S phase at rates similar to valproate (from 10.2% in the control to 0% in both complex 2 and valproate). Our data highlighted the potential anti-tumoral activity of valproate-Zn+2 complexes and their viability as proptotypes for new drugs.