Abstract

Abstract Oleuropein is one of the two main phenolic compounds derived from olive leaves. Numerous studies have found that the polyphenols contained in olive leaves possess strong antioxidant properties, and increase apoptosis in many types of cancer cells, suggesting its possible efficacy as an anti-cancer treatments. The purpose of our study was to examine the effects of oleuropein extract on cell growth and viability of the K562 human leukemia cell line, and to investigate possible molecular mechanisms of action. Oleuropein of 98% purity was used for our studies. We first demonstrated that K562 cells treated with 200 and 400 μg/ml oleuropein exhibited a significant reduction in cell growth and viability after four days as compared to ethanol-treated controls. Cells treated with 200μg/ml oleuropein showed decreased cell proliferation and viability after two days, and exhibited approximately 90% reduction in cell density and viability after four days of treatment. A concentration of 400 μg/ml oleuropein resulted in 100% toxicity by day four. We also examined the effects of oleuropein on cellular cytotoxicity using an LDH release assay and found a two-fold elevation in LDH release within 24 hours of treatment with 200 μg/mL oleuropein. To begin to explore a mechanisms of action, we used western blotting to examine known antioxidant and signaling pathways for possible regulation by oleuropein in these cells. We examined expression of the Peroxiredoxin (Prdx) family of proteins, a group of thiol-specific antioxidants found to be elevated in many types of cancer. We found that 200 ug/ml oleuropein reduced Prdx1 expression by about 50% after eight and twenty-four hours, while having no significant effect on expression levels of Prdx-2, -3, -4, and -6. We are currently investigating the mechanism of cell death induced by oleuropein, as well as the role of Prdx1 in oleuropein-induced toxicity. Together with previously reported cancer-cell specific effects, this research provides a promising new avenue for the use of natural products as anti-cancer agents. Citation Format: Natalie Fulco, Sophia Fagan, Shelley A. Phelan. Oleuropein reduces Prdx1 expression, cell proliferation and viability in K562 human leukemia cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1872.

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