Non-classical platinum-based compound 56MESS, with preferential cytotoxic effect on oral cancer cells by downregulating FACL4 expression.

Platinum (Pt)-based drugs are routinely used to treat oral cancer (OC), but occurrence of therapeutic resistance remains a formidable challenge in cancer treatment. We sought to explore the cytotoxicity of non-classical Pt-based compounds, and compared the efficacy and anticancer activity of 56MESS with cisplatin in OC. Drug sensitivity of seven non-classical Pt-based compounds as well as cisplatin were determined by CCK-8 assay. Comparison of cytotoxic effects between 56MESS, phenanthriplatin and cisplatin was performed on six different OC cell lines. The anticancer effects of 56MESS was further measured both and . Additionally, the biological role of FACL4 and its relationship with 56MESS-induced growth inhibition were investigated. Two out of seven Pt-based compounds displayed a significant cytotoxic effect. 56MESS was chosen as the most potent compound due to its highly selective cytotoxic activity. 56MESS particularly caused G2/M phase arrest, while failed to induce apoptosis. , 56MESS had a higher cytotoxic capacity than cisplatin. Overexpression of FACL4 rescued 56MESS-induced growth inhibition in OC cells. Overall, 56MESS is a highly selective and potent chemotherapeutic drug superior to cisplatin, and thus may be considered as a promising anticancer agent.