title: Diterpenylhydroquinones from natural ent-labdanes induce apoptosis through decreased mitochondrial membrane potential.
abstract: In this study, we examined the cytotoxic effects of seven ent-labdane derivatives 1-7 (0-100 μM) in different human cancer cell lines. Our results showed that compounds 1-3 exhibited significant dose-dependent inhibition on the growth of the three different human cell lines, according to the sulphorhodamine B assay and produced morphological changes consistent with apoptosis, as confirmed by Hoestch 3342 staining analysis. They induced apoptosis in various cancer cell lines, as shown by nuclear condensation and fragmentation and caspase 3 activation. Such induction was associated with the depletion of mitochondrial membrane potential. These activities led to the cleavage of caspases and the trigger of cell death process. Overall, the compounds showed potent proapoptotic effects on the two different cancer cell lines, suggesting that the compounds deserve more extensive investigation of their potential medicinal applications.
authors.affiliation: Centro de Investigaciones Biomédicas-CIB, Escuela de Medicina, Universidad de Valparaíso, Av. Hontaneda N° 2664, Valparaíso, Chile. juan.villena@uv.cl
authors.forename: Joan
authors.initials: J
authors.lastname: Villena
authors.forename: Alejandro
authors.initials: A
authors.lastname: Madrid
authors.forename: Iván
authors.initials: I
authors.lastname: Montenegro
authors.forename: Enrique
authors.initials: E
authors.lastname: Werner
authors.forename: Mauricio
authors.initials: M
authors.lastname: Cuellar
authors.forename: Luis
authors.initials: L
authors.lastname: Espinoza
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D003603:Cytotoxins / Q000737:chemistry / Q000494:pharmacology; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D009363:Neoplasm Proteins / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D004224:Diterpenes; D009363:Neoplasm Proteins; C505407:CASP3 protein, human; D053148:Caspase 3