Phytosterols in Physiological Concentrations Target Multidrug Resistant Cancer Cells

Blazej      Rubis; Anna      Polrolniczak; Hanna      Knula; Olga      Potapinska; Mariusz      Kaczmarek; Maria      Rybczynska

Abstract

Phytosterols have been proposed to act as potent anticancer agents. However the mechanism of their action has not been elucidated yet. Thus, the aim of our study was to determine whether plant sterols and their thermal processing products (in physiological concentration range) could influence the viability of cancer cells and thus could be considered as positive diet complements. Additionally we decided to study potential specificity of those natural compounds against cells showing high multidrug resistance. In this study we show that the cytotoxic effect of β-sitosterol was observed in both, estrogen-dependent and estrogen-independent cells. It was also shown that the β-sitosterol was significantly more cytotoxic in cells with basal ABCB1 expression (MCF7) than in multidrug resistant NCI/ADR-RES. Surprisingly, 5a,6aepoxysitosterol did not decrease the viability of any investigated cells but on the contrary, it provoked their increased proliferation. It was shown that oxyphytosterols blocked the cell cycle of MCF7 cells in G0/G1 phase while did not affect NCI/ADR-RES cell cycle in physiological concentration range. We also show that PgP activity (responsible for Multidrug Resistance phenomena) is inhibited by β-sitosterol. Thus, the phytosterols are supposed to act at various mechanisms but, what is most interesting, can target cells showing high multidrug resistance potential.

Keywords: ABCB1, beta-sitosterol, cancer, PgP, phytosterols, Multidrug Resistant Cancer Cells, anticancer agents, multidrug resistance, sitosterol, ABCB1 expression, oxyphytosterols, PgP activity, P-glycoprotein, ATP-binding cas-sette, estrogen, cardiovascular disease, sphingomyelin cy-cle, caspases, signal-transduction pathways, apoptosis, Liver cells, oxyphytosterols mixture, POLARIS Q mass spectrometer, Cell Culture, Cytotoxicity Assay, RPMI1640, DMEM medium, IC50 values, Propidium Iodide Staining, RNAse, flow cytometry, breast cancer cells, Verapamil, UV light microscopy, Student's t-test, MCF7 cells, MTT test, Colchicine, propidium iodide analysis, camptothecin, real-time PCR analysis, Rhodamine123, Caco-2, HepG2, MCF7, superoxide dismutase, glutathione peroxidase, mitochondrial enzymes activity, human stomach cancer cells