Cytotoxic and Apoptotic Effects of the Oxidized Derivatives of Stigmasterol in the U937 Human Monocytic Cell Line

Abstract

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 α-tocopherol, γ-tocopherol, and β-carotene did not protect against apoptosis induced by 7β-OH and diepoxide stigmasterol; however, α-tocopherol was found to protect against epoxydiol-induced apoptosis. The cellular antioxidant, glutathione, was depleted and the apoptotic protein, Bcl-2, was down-regulated by the stigmasterol oxides identified as apoptotic.

Phytosterol oxidation products in enriched foods: Occurrence, exposure, and biological effects

“…Numerous in vitro experiments incubating various cell types and cell lines with mixtures of oxides or synthesized pure oxides showed that POPs exert cytotoxic effects, which are qualitatively similar to those observed for cholesterol oxidation products, but higher concentrations were required (> 60 μM) . The assessment of markers indicative of inflammatory and/or apoptotic cellular mechanisms demonstrated a reduction of cell viability as well as the generation of oxidative stress and related processes thereof, 7‐ ß ‐hydroxy‐ and 7‐keto‐derivatives exhibiting the highest cytotoxic potential among those oxides dominating in foods.…”

Stigmasterol isolated from marine microalgae Navicula incerta induces apoptosis in human hepatoma HepG2 cells

“…According to the chemical formula, the C 29 H 48 O is evolved from the family of cholesterol. These kinds of phtytosterols are known to have an inductive effect of apoptosis in breast cancer, prostate cancer and human colon cancer cells (5 , 6 , 8 , 9) .…”

“…The plant-derived phytosterols are structurally similar to cholesterol with a double bond at the C 5-6 position (4) . Several previous studies reported that phytosterol has apoptosis inductive effects in some kinds of carcinoma cell lines such as human colon cancer cell (HT-29), human prostate cancer cell (LNCaP), human breast cancer cell (MDA-MB-231) (5 - 8) . Stigmasterol is also belongs to the group of phytosterol.…”

7α-Hydroxy-β-Sitosterol fromChisocheton tomentosusInduces Apoptosis via Dysregulation of Cellular Bax/Bcl-2 Ratio and Cell Cycle Arrest by Downregulating ERK1/2 Activation

“…In contrast, investigation on the mechanistic effects of phytosterol oxides is still scarce. Despite several reports on the cytotoxicity of these compounds, their cytotoxic mechanism of action is, however, still unclear [18, 27]. Roussi et al [28] suggested that 7 β -hydroxysitosterol, one of the many phytosterol oxides, could target the mitochondria, leading to loss of mitochondrial membrane potential to induce cytochrome c release.…”