Abstract
Background: Prostate cancer is one of the leading causes of cancer related deaths in males worldwide. Overexpression
of 15-lipoxygenase-1 (15-LOX-1) enzyme and high activity of its metabolic pathway is reported to be a driver for prostate
cancer malignancy. Farnesyloxycoumarin derivatives (3f, 4f and 7f) inhibit lipoxygenase enzyme. We hypothesized that
farnesyloxycoumarins may exert an anti-cancer effect on prostate cancer cells due to their 15-LOX-1 inhibitory potential.
Methods: The enzyme inhibitory activity of 3f, 4f and 7f was initially evaluated on PC-3 and DU145 prostate cancer cell lines. MTT
assay was performed on cancer cell lines and HFF3 cell line to assess cytotoxicity of the compounds. The apoptotic morphology
of cells after treatments was assessed by DAPI staining and single cell gel electrophoresis. Propidium iodide staining was also
performed to detect cell cycle variations after treatment.
Results: 7f inhibited 15-LOX-1 at IC50=4.3 µg/mL, while 3f and 4f did not show high inhibitory activity. 7f reduced cell viability
in PC-3 cells at IC50=22-31 µg/mL, however, no significant cytotoxicity was revealed on normal cells. DAPI staining and comet
assay confirmed apoptosis and DNA damage in PC-3 cells after 7f treatment, while flow cytometry results revealed G1 arrest in
PC-3 cells.
Conclusion: The results are indicative of a distinctive cytotoxic mechanism for 7f compared to other coumarins, possibly due to
its 15-LOX-1 inhibitory potential. Thus, this compound is valued for further assessments with the aim of developing a promising
targeted therapy for prostate cancer patients