title: 13-Hydroxy-15-oxo-zoapatlin, an ent-kaurane diterpene, induces apoptosis in human leukemia cells, affecting thiol-mediated redox regulation.
abstract: 13-Hydroxy-15-oxo-zoapatlin (OZ), a nor-kaurane diterpene, was first described as a compound inhibiting the proliferation of human cancer cell lines. Successively, it was reported that OZ inhibits the G2 DNA damage checkpoint and causes mitotic arrest. To get more insight into the molecular mechanism(s) underlying the antitumor potential of OZ, we evaluated the proapoptotic activity of this molecule. OZ was found to induce hypodiploidia and phosphatidylserine externalization, two hallmarks of apoptosis; to disrupt mitochondrial membrane potential; and to trigger caspase-3 activation. OZ-induced cell death, mostly dependent upon the presence of the alpha,beta-carbonyl group, is strongly related to alterations in the cellular redox balance. The interaction of OZ with cellular components and proteins containing reactive thiols was evaluated by mass spectrometry-based approaches. A specific reactivity of this compound toward glutathione and thioredoxin was observed.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Salerno, Via Ponte Don Melillo, 84084 Fisciano, Salerno, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Dal Piaz
authors.forename: Patrizia
authors.initials: P
authors.lastname: Nigro
authors.forename: Alessandra
authors.initials: A
authors.lastname: Braca
authors.forename: Nunziatina
authors.initials: N
authors.lastname: De Tommasi
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Belisario
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004171:Diploidy; D004224:Diterpenes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D045786:Diterpenes, Kaurane / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007938:Leukemia; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010084:Oxidation-Reduction; D010718:Phosphatidylserines / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: C099329:13-hydroxy-15-oxozoapatlin; D000970:Antineoplastic Agents; D004224:Diterpenes; D045786:Diterpenes, Kaurane; D010718:Phosphatidylserines; D013438:Sulfhydryl Compounds; D013879:Thioredoxins; D053148:Caspase 3; D005978:Glutathione