Involvement of the PI3K/AKT Intracellular Signaling Pathway in the AntiCancer Activity of Hydroxytyrosol, a Polyphenol from Olea europaea, in Hematological Cells and Implication of HSP60 Levels in Its Anti-Inflammatory Activity
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AuteurParra Pérez, Alberto M.; Pérez Jiménez, Amalia; Gris Cárdenas, Isabel; Bonel Pérez, Gloria C.; Carrasco Díaz, Luis M.; Mokhtari, Khalida; García Salguero, Encarnación Leticia; Lupiáñez Cara, José Antonio; Rufino Palomares, Eva
ApoptosisCell cycle arrestHSP60HydroxytyrosolInflammationLeukemia cellsPI3K/AKT signaling pathwayROS level
Parra-Perez, A.M... [et al.]. Involvement of the PI3K/AKT Intracellular Signaling Pathway in the AntiCancer Activity of Hydroxytyrosol, a Polyphenol from Olea europaea, in Hematological Cells and Implication of HSP60 Levels in Its Anti-Inflammatory Activity. Int. J. Mol. Sci. 2022, 23, 7053. [https://doi.org/10.3390/ijms23137053]
PatrocinadorGeneral Secretariat of Universities, Research and Technology of the Ministry of Economy, Innovation, Science and Employment of the Government of the Junta de Andalucia, Spain BIO-157
Hydroxytyrosol (HT), the main representative of polyphenols of olive oil, has been described as one of the most powerful natural antioxidants, also showing anti-inflammatory, antimicrobial, cardioprotective and anticancer activity in different type of cancers, but has been little studied in hematological neoplasms. The objective of this work was to evaluate the anticancer potential of HT in acute human leukemia T cells (Jurkat and HL60) and the anti-inflammatory potential in murine macrophages (Raw264.7). For this, cytotoxicity tests were performed for HT, showing IC50 values, at 24 h, for Jurkat, HL60 and Raw264.7 cells, of 27.3 mu g center dot mL(-1), 109.8 mu g center dot mL(-1) and 45.7 mu g center dot mL(-1), respectively. At the same time, HT caused cell arrest in G(0)/G(1) phase in both Jurkat and HL60 cells by increasing G(0)/G(1) phase and significantly decreasing S phase. Apoptosis and cell cycle assays revealed an antiproliferative effect of HT, decreasing the percentage of dividing cells and increasing apoptosis. Furthermore, HT inhibited the PI3K signaling pathway and, consequently, the MAPK pathway was activated. Inflammation tests revealed that HT acts as an anti-inflammatory agent, reducing NO levels in Raw264.7 cells previously stimulated by lipopolysaccharide (LPS). These processes were confirmed by the changes in the expression of the main markers of inflammation and cancer. In conclusion, HT has an anticancer and anti-inflammatory effect in the cell lines studied, which were Raw264.7, Jurkat, and HL60, and could be used as a natural drug in the treatment of liquid cancers, leukemias, myelomas and lymphomas.