title: Tempranillo-derived grape seed extract induces apoptotic cell death and cell growth arrest in human promyelocytic leukemia HL-60 cells.
abstract: Although grape seed extract (GSE) has proven to be effective against various cancers, few studies have investigated the effects of GSE on human leukemia. In this study, we analysed the mechanisms involved in the apoptotic effects induced by GSE on human promyelocytic leukemia HL-60 cells. Thus, GSE treatment succeeded in activating caspase-3 (P < 0.05), the activation being dose-dependent and time-dependent. Activation of caspase-3 induced by GSE was accompanied by mitochondrial membrane depolarization (P < 0.05). Moreover, disruption of mitochondrial integrity caused by GSE treatment subsequently led to activation of caspase-9 (P < 0.05), and also produced a slight increase in ROS levels (P < 0.05). Cytotoxic effects elicited by GSE treatment ultimately resulted in extensive S-phase arrest (P < 0.05) and a substantial increase in the intrinsic rate of apoptosis (P < 0.05). Our findings suggest that the GSE induces apoptotic cell death and cell growth inhibition in human leukemic HL-60 cells, which seems to be dependent on mitochondrial damage. Therefore, the GSE obtained from Tempranillo cultivars could be an effective approach to restrain uncontrolled cell proliferation and survival in leukemia cells.
authors.affiliation: Department of Physiology, Neuroimmunophysiology and Chrononutrition Research Group, Faculty of Science, University of Extremadura, 06006 Badajoz, Spain. jespino@unex.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Espino
authors.forename: David
authors.initials: D
authors.lastname: González-Gómez
authors.forename: Daniel
authors.initials: D
authors.lastname: Moreno
authors.forename: María F
authors.initials: MF
authors.lastname: Fernández-León
authors.forename: Ana B
authors.initials: AB
authors.lastname: Rodríguez
authors.forename: José A
authors.initials: JA
authors.lastname: Pariente
authors.forename: Jonathan
authors.initials: J
authors.lastname: Delgado-Adámez
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D056604:Grape Seed Extract / Q000008:administration & dosage*; D018922:HL-60 Cells; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D027843:Vitis / Q000737:chemistry*
chemical_list: D056604:Grape Seed Extract; D017382:Reactive Oxygen Species; D053148:Caspase 3; D053453:Caspase 9