Ketoplatin in triple-negative breast cancer cells MDA-MB-231: High efficacy and low toxicity, and positive impact on inflammatory microenvironment.

Triple-negative breast cancer (TNBC) shares the molecular features facilitating epithelial-to-mesenchymal transition (EMT), which contributed to tumor invasion and metastasis. A platinum(IV) conjugate ketoplatin deriving from FDA-approved drugs cisplatin and ketoprofen was designed and prepared to enhance antitumor activity and suppress EMT in TNBC via positive impact on inflammatory microenvironment by modulating COX-2 signal. As a prodrug, ketoplatin afforded 50.

New NSAID-Pt(IV) prodrugs to suppress metastasis and invasion of tumor cells and enhance anti-tumor effect in vitro and in vivo.

The great interest in epithelial-to-mesenchymal transition (EMT) programme lies in its association with process of metastasis and invasion, which is a crucial cause of cancer-related death. Herein, we designed and reported three new NSAID-Pt(IV) prodrugs, taking Non-Steroid Anti-Inflammatory Drugs (NSAIDs) to disrupt EMT programme and assist genotoxic platinum-based drugs as a cytotoxicity booster, to offer a class of potential anticarcinogens with a multi-functional action mechanism. The NSAID-Pt(IV) prodrugs, especially Eto-Pt(IV), highly enhanced cellular uptake with amount up to 42-fold at 3 h compared with CDDP, and greatly increased DNA damage and cell apoptosis, showing much higher cytotoxicity than cisplatin in the tested cancer cells even in A549/cis cells.