cisplatin + silibinin

**Cisplatin + silibinin** is a combination of cisplatin, a platinum-based alkylating chemotherapeutic agent, and silibinin, a polyphenolic flavonoid from milk thistle (Silybum marianum) with chemopreventive properties. Cisplatin forms DNA intra- and interstrand cross-links, inhibiting replication and transcription, leading to cell death in rapidly dividing cancer cells, while silibinin enhances these effects by promoting G2-M cell cycle arrest, increasing expression of cell cycle regulators like Chk1 and Wee1, and boosting apoptosis via caspase activation and cytochrome c release. The combination demonstrates strong synergy in preclinical models of prostate, breast, and lung cancers, overcoming resistance, enhancing growth inhibition (e.g., 48% to 80% in DU145 cells), and reducing cisplatin-induced nephrotoxicity without compromising antitumor activity.[1][2][5]