Phytosterols in physiological concentrations target multidrug resistant cancer cells

• Published in: Medicinal chemistry (Shp-sariqah, United Arab Emirates) Vol. 6; no. 4; p. 184
• Main Authors: Rubis, Blazej, Polrolniczak, Anna, Knula, Hanna, Potapinska, Olga, Kaczmarek, Mariusz, Rybczynska, Maria
• Format: Journal Article
• Language: English
• Published: Netherlands 01.07.2010
• Subjects: Antineoplastic Agents - pharmacology; ATP-Binding Cassette, Sub-Family B, Member 1 - antagonists & inhibitors; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Cycle - drug effects; Cell Survival - drug effects; Dose-Response Relationship, Drug; Drug Resistance, Multiple - drug effects; Drug Resistance, Neoplasm - drug effects; Humans; Phytosterols - pharmacology; Structure-Activity Relationship; Tumor Cells, Cultured; Verapamil - pharmacology
• ISSN: 1875-6638
• DOI: 10.2174/1573406411006040184

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,6a-epoxysitosterol 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.