Overexpression of 15-lipoxygenase-1 (15-LOX-1)
enzyme has been reported in prostate
tumors, and its expression levels are associated with the degree of
cancer malignancy. The aim of this study was to investigate inhibitory effects of
stylosin and some similar synthetic
monoterpenoids on 15-LOX and also their cytotoxic and anti-
cancer activities on
prostate cancer cells. Cytotoxicity of compounds was evaluated on
prostate cancer cell line "PC-3" and normal human fibroblast "HFF3" cells using
AlamarBlue reduction test. The inhibitory effects of the compounds against soybean 15-LOX, a commercially available
enzyme, were also assessed. Finally, mechanism of cell death was investigated by flow cytometry. Some of these
terpenoids had cytotoxic effects on PC-3 cells, and strong positive correlation was observed between the 15-LOX-1 inhibition potential and the cytotoxicity of the compounds. Moreover, flow cytometry results indicated that apoptosis was the predominant mechanism of induced cell death, which emphasizes the potential of these compounds in
prostate cancer therapy. Among studied
terpenoids, "fenchyl ferulate" exhibited about three times more cytotoxicity than
cisplatin. Strong positive correlation observed between 15-LOX inhibition potential and cytotoxicity of the compounds indicates selective anti-
cancer properties of the compounds might be exerted via inhibition of 15-LOX-1 in PC-3 cells. Furthermore, observed cytotoxicity is mediated through apoptosis, which is probably triggered via 15-LOX-1 inhibition.