title: Cytotoxic effects of natural and semisynthetic cucurbitacins on lung cancer cell line A549.
abstract: Cucurbitacins and their derivatives are triterpenoids that are found in various plant families, and are known for their pharmacological and biological activities, including anti-cancer effects. Lung cancer represents a major public health problem, with non-small-cell lung cancer (NSCLC) being the most frequent and aggressive type of lung cancer. The objective of this work was to evaluate four cucurbitacins (CUCs) for their cytotoxic activity, effects on apoptosis induction, cell cycle progression, anti-migratory, and anti-invasive effects on the human NSCLC cell line (A549 cells). Our findings showed that these CUCs could suppress human NSCLC cell growth in vitro through their effects on the PI3Kinase and MAPK pathways, which lead to programmed cell death induction, as well as inhibition of cell migration and cell invasion. Additionally, these effects culminate in apoptosis induction and G2/M cell cycle arrest by modulating cyclin B1 expression, and in the mitigation of strategic steps of lung cancer metastasis, including migration and invasion of A549 cells. These results suggest that two natural (DDCB and CB) and two novel semisynthetic derivatives of cucurbitacin B (ACB and DBCB) could be considered as promising compounds with antitumor potential.
authors.affiliation: Departamento de Ciências Farmacêuticas, CIF, CCS, Universidade Federal de Santa Catarina (UFSC), Campus Universitário Trindade, Florianópolis, 88040-900, SC, Brazil.
authors.forename: Izabella Thaís
authors.initials: IT
authors.lastname: Silva
authors.affiliation: Departamento de Ciências Farmacêuticas, CIF, CCS, Universidade Federal de Santa Catarina (UFSC), Campus Universitário Trindade, Florianópolis, 88040-900, SC, Brazil.
authors.forename: Fabiana Cristina
authors.initials: FC
authors.lastname: Geller
authors.affiliation: Departamento de Ciências Farmacêuticas, CIF, CCS, Universidade Federal de Santa Catarina (UFSC), Campus Universitário Trindade, Florianópolis, 88040-900, SC, Brazil.
authors.forename: Lara
authors.initials: L
authors.lastname: Persich
authors.affiliation: Institute of Molecular Virology, Center of Molecular Biology of Inflammation, Westfaelische-Wilhelms-University, Muenster, Germany.
authors.forename: Sabine Eva
authors.initials: SE
authors.lastname: Dudek
authors.affiliation: Department of Chemistry, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Karen Luise
authors.initials: KL
authors.lastname: Lang
authors.affiliation: Department of Chemistry, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Miguel Soriano Balparda
authors.initials: MS
authors.lastname: Caro
authors.affiliation: UMYMFOR - Department of Organic Chemistry, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Fernando Javier
authors.initials: FJ
authors.lastname: Durán
authors.affiliation: Departamento de Ciências Farmacêuticas, CIF, CCS, Universidade Federal de Santa Catarina (UFSC), Campus Universitário Trindade, Florianópolis, 88040-900, SC, Brazil.
authors.forename: Eloir Paulo
authors.initials: EP
authors.lastname: Schenkel
authors.affiliation: Institute of Molecular Virology, Center of Molecular Biology of Inflammation, Westfaelische-Wilhelms-University, Muenster, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Ludwig
authors.affiliation: Departamento de Ciências Farmacêuticas, CIF, CCS, Universidade Federal de Santa Catarina (UFSC), Campus Universitário Trindade, Florianópolis, 88040-900, SC, Brazil. claudia.simoes@ufsc.br.
authors.forename: Cláudia Maria Oliveira
authors.initials: CM
authors.lastname: Simões
mesh_terms: D000072283:A549 Cells; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D054728:Cucurbitacins / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D056744:Cyclin B1 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D056744:Cyclin B1; D014409:Tumor Necrosis Factor-alpha; D054728:Cucurbitacins; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020169:Caspases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Apoptosis; Cucurbitacins; Invasion; Metastasis