{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T02:18:27Z","timestamp":1777515507922,"version":"3.51.4"},"reference-count":65,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T00:00:00Z","timestamp":1656028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the consolidated Research Group BIO-157, \u201cDrugs, environmental toxicants and cellular metabolism\u201d"},{"name":"the General Secretariat of Universities, Research and Technology of the Ministry of Economy, Innovation, Science and Employment of the Government of the Junta de Andaluc\u00eda, Spain"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u00b5g\u00b7mL\u22121, 109.8 \u00b5g\u00b7mL\u22121 and 45.7 \u00b5g\u00b7mL\u22121, 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.<\/jats:p>","DOI":"10.3390\/ijms23137053","type":"journal-article","created":{"date-parts":[[2022,6,26]],"date-time":"2022-06-26T09:00:13Z","timestamp":1656234013000},"page":"7053","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["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"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1208-8348","authenticated-orcid":false,"given":"Alberto M.","family":"Parra-Perez","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Avenida Fuentenueva, 1, 18071 Granada, Spain"},{"name":"GENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada, Avenida de la Ilustraci\u00f3n, 114, 18016 Granada, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9971-8623","authenticated-orcid":false,"given":"Amalia","family":"P\u00e9rez-Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Department of Zoology, Faculty of Sciences, University of Granada, Avenida Fuentenueva, 1, 18071 Granada, Spain"}]},{"given":"Isabel","family":"Gris-C\u00e1rdenas","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Avenida Fuentenueva, 1, 18071 Granada, Spain"},{"name":"CIC bioGUNE, Centre for Cooperative Research in Biosciences, 48160 Derio, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6546-3039","authenticated-orcid":false,"given":"Gloria C.","family":"Bonel-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Avenida Fuentenueva, 1, 18071 Granada, Spain"},{"name":"CNIO, Spanish National Cancer Research Centre, Calle Melchor Fern\u00e1ndez Almagro, 3, 28029 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0567-2802","authenticated-orcid":false,"given":"Luis M.","family":"Carrasco-D\u00edaz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Avenida Fuentenueva, 1, 18071 Granada, Spain"},{"name":"Sant Pau Hospital Research Institute Foundation, Autonomous University of Barcelona (UAB), 08193 Barcelona, Spain"}]},{"given":"Khalida","family":"Mokhtari","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Avenida Fuentenueva, 1, 18071 Granada, Spain"},{"name":"Laboratory of Bioresources, Biotechnologies, Ethnopharmacology and Health, Department of Biology, Faculty of Sciences, Mohammed I University, Oujda 60000, Morocco"}]},{"given":"Leticia","family":"Garc\u00eda-Salguero","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Avenida Fuentenueva, 1, 18071 Granada, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9095-7145","authenticated-orcid":false,"given":"Jos\u00e9 A.","family":"Lupi\u00e1\u00f1ez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Avenida Fuentenueva, 1, 18071 Granada, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9650-825X","authenticated-orcid":false,"given":"Eva E.","family":"Rufino-Palomares","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Avenida Fuentenueva, 1, 18071 Granada, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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