Cytotoxic activity of stigmasteryl esters and products of their thermo-oxidative degradation against drug sensitive and drug resistant human acute lymphoblastic leukemia cells

Abstract

Background. Phytosterols are mainly known as a cholesterol-lowering factor, although they form oxidation products during food storage and processing. Moreover, phytosterol oxidation products (POP) can be absorbed and found in human serum, so there is the need to investigate their impact on different kinds of cells. Material and methods. Esters of fatty acids (oleic, linoleic and linolenic) with stigmasterol were synthetized and heated at 180°C, for 1-12 hours. The cytotoxic effect on the leukemic cells of unheated stigmasteryl esters and the mixture of compounds after heating was determined using MTT assays. POP were identified using GC-MS. The total number of POP was analysed by SPE fractionation and GC-FID separation. Dimers, trimers and oligomers in non-polar fraction were determined by gel permeation chromatography with refractive index detection. Results. After heating, stigmasterol oxidation products were formed (up to 1.1 mg/g ester). The heating increased the potency of the compounds to reduce cell population and form POPs and oligomers in a timedependent manner. Conclusion. The cytotoxicity depends on the kind of ester, dose and time. The strongest cytotoxic effect was found after 72 hours of cell treatment. Among the three stigmasteryl esters tested the most cytotoxic effect was caused by stigmasteryl linoleate.

Anti-proliferative potential and oxidative reactivity of thermo-oxidative degradation products of stigmasterol and stigmasteryl esters for human intestinal cells

“…The heated ST-OA did not induce cytotoxic and genotoxic effects nor elevate the intracellular ROS level in normal human colon cells. Similarly, the different cytotoxic potency of thermally treated ST-LA and ST-OA was also observed in human acute lymphoblastic leukemia cell cultures 38 . The higher ST-LA reactivity was probably due to the 2.3-fold higher content of SOPs 25 .…”

“…Previous studies have shown that free ST is degraded rapidly, generating a diverse group of thermo-oxidative degradation products and oxyderivatives 21 , 25 which may exhibit significant oxidative reactivity and induce cytotoxic and genotoxic effects in normal human cells as demonstrated in the presented studies. It was found that ST esterification with oleic and linoleic acids limited ST degradation and the formation of oxidized sterols, degradation products, and oligomers 25 , 38 , leading to a reduction in the risk of adverse toxic effects. Cytotoxicity experiments proved the lower cytotoxic potential of stigmasteryl esters (ST-OA and ST-LA) than free ST, regardless of whether they were subjected to thermo-oxidative treatment.…”

Advances in Stigmasterol on its anti-tumor effect and mechanism of action

“…Raczyk et al. ( 80 ) examined the cytotoxic effect of three stigmasteryl esters on leukemia cells using MTT assay, and they found that the stigmasteryl linoleate had the greatest cytotoxic effect. Nazemi et al.…”