Cytotoxic and apoptotic effects of the oxidized derivatives of stigmasterol in the u937 human monocytic cell line

Dietary exposure to phytosterols has increased in recent years due to the incorporation of these compounds into cholesterol-lowering products. Previous studies have investigated the cytotoxic effects of the oxidized derivatives of β-sitosterol and determined that phytosterol oxidation products (POP) have a similar but less potent toxicity compared to their cholesterol equivalents. In the present study, the cytotoxicity of the oxidized derivatives of stigmasterol were investigated in the U937 cell line. The stigmasta-5,22-diene-3β, 7β-diol (7β-OH), 5,6-epoxystigmasta-22,23-diol (epoxydiol), 5,6,22,23-diepoxystigmastane (diepoxide), and (22R,23R)-stigmast-5-ene-3β, 22,23-triol (22R,23R-triol) derivatives were identified as the most cytotoxic, and the mode of cell death was identified as apoptosis in cells incubated with 7β-OH, epoxydiol, and diepoxide stigmasterol. The antioxidants R-tocopherol, γ-tocopherol, and β-carotene did not protect against apoptosis induced by 7β-OH and diepoxide stigmasterol; however, R-tocopherol was found to protect against epoxydiolinduced apoptosis. The cellular antioxidant, glutathione, was depleted and the apoptotic protein, Bcl-2, was down-regulated by the stigmasterol oxides identified as apoptotic.