title: Enhanced chemopreventive activity of hydroxytyrosol on HL60 and HL60R cells by chemical conversion into thio derivatives.
abstract: Thio derivatives of hydroxytyrosol containing thiol, thioacetate and disulfide functionalities were synthesized from natural hydroxytyrosol (3,4-DHPEA) via 3,4-dihydroxyphenethyl halides. These compounds, containing the combination of catechol moiety and divalent sulfur functions, were tested for the pro-apoptotic and anti-proliferative activities on both parental HL60 and multi-drug resistant HL60R cells. It was found that all synthesized compounds were more effective than 3,4-DHPEA in inducing apoptosis on HL60R cells, and that the hydroxytyrosol disulfide was the most active pro-apoptotic and anti-proliferative compound on both HL60 and HL60R cells. Different from 3,4-DHPEA, all thio derivatives of hydroxytyrosol induced apoptosis by a mechanism not involving the release of H(2)O(2) in the culture medium. The data on HL60R cells suggest that these compounds could be able to reverse the resistance toward the most common drugs in cancer therapy.
authors: Dipartimento di Specialità Medico Chirurgiche e Sanità Pubblica, Sezione di Epidemiologia Molecolare e Igiene Ambientale, Università di Perugia, Via del Giochetto, 06126 Perugia, Italy.
authors: Maria Vittoria
authors: MV
authors: Sepporta
authors: M Ángeles
authors: MÁ
authors: López-García
authors: Roberto
authors: R
authors: Fabiani
authors: Inés
authors: I
authors: Maya
authors: José G
authors: JG
authors: Fernández-Bolaños
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013457:Sulfur Compounds / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D013457:Sulfur Compounds; C005975:3,4-dihydroxyphenylethanol; D006861:Hydrogen Peroxide; D010626:Phenylethyl Alcohol