title: Hecogenin acetate inhibits reactive oxygen species production and induces cell cycle arrest and senescence in the A549 human lung cancer cell line.
abstract: Cellular and molecular mechanisms related to lung cancer have been extensively studied in recent years, but the availability of effective treatments is still scarce. Hecogenin acetate, a natural saponin presenting a wide spectrum of reported pharmacological activities, has been previously evaluated for its anticancer/antiproliferative activity in some in vivo and in vitro models. Here, we investigated the effects of hecogenin acetate in a human lung cancer cell line. A549 non-small lung cancer cells were exposed to different concentrations of hecogenin acetate and reactive species production, ERK1/2 activation, matrix metalloproteinase expression, cell cycle arrest and cell senescence parameters were evaluated. Hecogenin acetate significantly inhibited increase in intracellular reactive species production induced by H2O2. In addition, hecogenin acetate blocked ERK1/2 phosphorylation and inhibited the increase in MMP-2 caused by H2O2. Treatment with hecogenin acetate induced G0/G1-phase arrest at two concentrations (75 and 100 µM, 74% and 84.3% respectively), and increased the staining of senescence-associated β -galactosidase positive cells. These data indicate that hecogenin acetate is able to exert anti-cancer effects by modulating reactive species production, inducing cell cycle arrest and senescence and also modulating ERK1/2 phosphorylation and MMP-2 production.
authors.forename: Juciano
authors.initials: J
authors.lastname: Gasparotto
authors.forename: Nauana
authors.initials: N
authors.lastname: Somensi
authors.forename: Alice
authors.initials: A
authors.lastname: Kunzler
authors.forename: Carolina Saibro
authors.initials: CS
authors.lastname: Girardi
authors.forename: Matheus Augusto
authors.initials: MA
authors.lastname: de Bittencourt Pasquali
authors.forename: Vitor Miranda
authors.initials: VM
authors.lastname: Ramos
authors.forename: Andre
authors.initials: A
authors.lastname: Simoes-Pires
authors.forename: Lucindo Jose
authors.initials: LJ
authors.lastname: Quintans-Junior
authors.forename: Alexsandro
authors.initials: A
authors.lastname: Branco
authors.forename: Jose Claudio Fonseca
authors.initials: JC
authors.lastname: Moreira
authors.affiliation: Street Address: Rua Ramiro Barcelos, 2600 - anexo, CEP 90035-003, Porto Alegre, RS, Brazil. Juciano.gasparotto@gmail.com.
authors.forename: Daniel Pens
authors.initials: DP
authors.lastname: Gelain
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013141:Spiro Compounds / Q000494:pharmacology*; D013256:Steroids / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D013141:Spiro Compounds; D013256:Steroids; C505698:hecogenin acetate; D048049:Extracellular Signal-Regulated MAP Kinases; D020778:Matrix Metalloproteinase 2