title: (S)-Goniothalamin induces DNA damage, apoptosis, and decrease in BIRC5 messenger RNA levels in NCI-H460 cells.
abstract: (R)-Goniothalamin (R-GNT) is a secondary metabolite isolated from the plants of the genus Goniothalamus. This molecule has attracted the attention of researchers because of its selective cytotoxicity against tumor cells and its ability to induce apoptosis. (S)-Goniothalamin (S-GNT) is a synthetic enantiomer of R-GNT, and its mechanism of action is largely unknown. In this study, we investigated the activity of S-GNT in a human non-small cell lung cancer NCI-H460 cells. We observed that the cells exposed to this compound exhibited cytotoxicity in a concentration-dependent manner. Based on the data obtained through the assessment of apoptosis induction in situ and the comet assay, we suggest that this cytotoxicity occurs due to the potential ability of this molecule to induce DNA damage with the consequent induction of cell death via apoptosis. A significant reduction in the messenger RNA levels of baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) gene that encodes the survivin protein was found. This novel finding may explain the inhibition of cell proliferation and induction of apoptosis in tumor cells caused by this compound.
authors.affiliation: 1Departamento de Biologia Geral, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
authors.forename: S C
authors.initials: SC
authors.lastname: Semprebon
authors.forename: Â
authors.initials: Â
authors.lastname: de Fátima
authors.forename: S R
authors.initials: SR
authors.lastname: Lepri
authors.forename: D
authors.initials: D
authors.lastname: Sartori
authors.forename: L R
authors.initials: LR
authors.lastname: Ribeiro
authors.forename: M S
authors.initials: MS
authors.lastname: Mantovani
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D007928:Lethal Dose 50; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011753:Pyrones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D013237:Stereoisomerism; D000077022:Survivin
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D011753:Pyrones; D012333:RNA, Messenger; D000077022:Survivin; C103280:goniothalamin
keywords: (S)-goniothalamin; Apoptosis; BIRC5; cytotoxicity; genotoxicity; survivin