The impact of 15-lipoxygenase-1 (15-LOX-1) in the progression of prostate cancer (PCa) is noteworthy, as it correlates with the Gleason score of the disease. Thus, development of specific 15-LOX-1 inhibitors would be desirable for targeted therapy of PCa. This study focused on evaluating the anti-prostate cancer potency of three farnesyloxycarbostyril derivatives, 6-, 7- and 8-farnesyloxycarbostyril (6-, 7- and 8-FQ), as potential inhibitors of 15-LOX-1 on PCa cells. To this end, the enzymatic activity of 15-LOX was first assessed in PCa and human dermal fibroblast (HDF) cells. Subsequently, the cytotoxic effects and apoptosis-inducing capabilities of the compounds were assessed through MTT assay and FITC-annexin V/PI staining, respectively. Among the compounds, 8-FQ was selected for further assessment in a mouse model bearing xenograft human PCa tumor. The results demonstrated that the most effective compound, 8-FQ, caused an 84-fold and 15.7-fold reduction in 15-LOX activity in PC-3 cells at 30 and 14 μM concentrations, respectively. The MTT assay revealed a dose- and time dependent toxicity of the compounds on PCa cells, and flow cytometry results indicated that apoptosis served as the dominant mechanism of cell death. Given the upregulation of 15-LOX-1 in human PCa cells, the study concludes that the heightened sensitivity to 8-FQ is likely associated with elevated levels of 15-LOX-1. In vivo experiments using immunosuppressed C57BL/6 mice bearing human PC-3 tumors revealed that 8-FQ, at a dosage of 10 mg/kg, exhibited strong antitumor effects with minimal side effects, indicating its potential as a promising therapeutic agent for PCa following further optimization.

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