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
Parra-Perez, Alberto M. (GENYO. Centre for Genomics and Oncological Research: Pfizer. Universidad de Granada)
Pérez-Jiménez, Amalia (Universidad de Granada. Departamento de Zoología. Facultad de Ciencias)
Gris-Cárdenas, Isabel (CIC bioGUNE. Centre for Cooperative Research in Biosciences)
Bonel-Pérez, Gloria C. (Centro Nacional de Investigaciones Oncológicas Carlos III (Espanya))
Carrasco-Díaz, Luis Miguel (Institut d'Investigació Biomèdica Sant Pau)
Mokhtari, khalida (Mohammed I University. Laboratory of Bioresources. Biotechnologies. Ethnopharmacology and Health. Department of Biology. Faculty of Sciences)
García-Salguero, Encarnacion Leticia (Universidad de Granada. Departamento de Bioquímica y Biología Molecular I)
Lupiáñez, José Antonio (Universidad de Granada. Departamento de Bioquímica y Biología Molecular I)
Rufino-Palomares, Eva E. (Universidad de Granada. Departamento de Bioquímica y Biología Molecular I)
Universitat Autònoma de Barcelona

Fecha:	2022
Resumen:	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 µg·mL, 109. 8 µg·mL and 45. 7 µg·mL, respectively. At the same time, HT caused cell arrest in G0/G1 phase in both Jurkat and HL60 cells by increasing G0/G1 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.
Nota:	Altres ajuts: Secretaría General de Universidades, Investigación y Tecnología de la Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Apoptosis ; Cell cycle arrest ; HSP60 ; Hydroxytyrosol ; Inflammation ; Leukemia cells ; PI3K/AKT signaling pathway ; ROS level
Publicado en:	International journal of molecular sciences, Vol. 23 Núm. 13 (july 2022) , p. 7053, ISSN 1422-0067

DOI: 10.3390/ijms23137053
PMID: 35806065

21 p, 2.8 MB

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