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 in vitro and in vivo. 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. In vivo, 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.