Anticancer effects of ruthenium-sorafenib complexes in prostate cancer cell lines

Aims: To evaluate the cytotoxic and pro-apoptotic activities of newly synthesized ruthenium–sorafenib complexes (Ru1S–Ru8S) in prostate cancer models and to identify a lead candidate for advanced/castration-resistant prostate cancer. Methods: Ru1S–Ru8S were synthesized as previously described. Cytotoxicity was assessed by MTT in PC3, DU145, LNCaP, and, CCD1079Sk cells after 24 and 48 h exposure to 0.2–100 µM compounds; IC₅₀ values were calculated versus untreated controls. Apoptosis was analyzed in PC3 cells by Annexin V/7-AAD staining and flow cytometry after treatment with Ru1S, Ru3S, Ru4S, or sorafenib at graded concentrations. Molecular modelling examined potential binding interactions of Ru1S. Results: The complexes displayed cell line- and time-dependent cytotoxicity. At 48 h, Ru1S and Ru4S were among the most active complexes in cancer cells. Ru4S achieved the highest potency in cancer cells but was associated with extensive cell death displaying features consistent with both apoptotic and non-apoptotic processes. Ru1S induced prominent late-stage apoptosis in PC3 cells (comparable to Ru3S) while maintaining substantially lower toxicity in CCD-1079Sk cells. Sorafenib, although highly potent, exhibited considerable toxicity toward CCD-1079Sk cells. Modelling supported an androgen receptor–independent effect for Ru1S.Conclusion: Ruthenium coordination modulates sorafenib-driven cell-death pathways and may improve in vitro selectivity profiles compared with sorafenib. Ru1S emerged as a lead candidate for further preclinical evaluation in castration-resistant prostate cancer, based on its pro-apoptotic activity in PC3 cells and comparatively lower cytotoxicity in CCD-1079Sk fibroblasts relative to sorafenib.