title: Cytotoxic effect of Erythroxylum daphnites extract is associated with G1 cell cycle arrest and apoptosis in oral squamous cell carcinoma.
abstract: Plant-derived molecules showing antineoplastic effects have recently gained increased attention as potential adjuvants to traditional therapies for various cancers. Cerrado biome in Brazil contains high floral biodiversity, but knowledge about the potential therapeutic effects of compounds derived from that flora is still limited. The present study investigated the antineoplastic activity of Erythroxylum daphnites Mart., a Brazilian native plant from Cerrado biome, in the SCC-9 oral squamous cell carcinoma cell line. Cells were treated with various concentrations of hexane extract of Erythroxylum daphnites leaves (EDH) and assessed for cytotoxicity, proliferation, and apoptosis. Thin layer chromatography was conducted to characterize the substances present in EDH. Our results showed that EDH exerted anti-proliferative effects in SCC-9 cells by stabilizing the cell cycle at G1 phase in association with reduced intracellular levels of cyclins D and E and increased level of p21. EDH also demonstrated pro-apoptotic properties, as shown by an increased expression of caspase-3. Triterpenes were the major constituents of EDH. Our findings demonstrated a cytotoxic effect of EDH against SCC-9 cells in vitro mediated by the restraint of cellular proliferation and induction of apoptosis. Taken together, these findings support EDH constituents as potential therapeutic adjuvants for oral cancer.
authors.affiliation: a Faculty of Health Sciences, University of Brasília , Brasília , Brazil.
authors.forename: Silvia T
authors.initials: ST
authors.lastname: Elias
authors.affiliation: b Faculty of Dentistry, University of Campinas , Piracicaba , São Paulo , Brazil.
authors.forename: Carolina C S
authors.initials: CC
authors.lastname: Macedo
authors.affiliation: a Faculty of Health Sciences, University of Brasília , Brasília , Brazil.
authors.forename: Luiz A
authors.initials: LA
authors.lastname: Simeoni
authors.affiliation: a Faculty of Health Sciences, University of Brasília , Brasília , Brazil.
authors.forename: Dâmaris
authors.initials: D
authors.lastname: Silveira
authors.affiliation: a Faculty of Health Sciences, University of Brasília , Brasília , Brazil.
authors.forename: Pérola O
authors.initials: PO
authors.lastname: Magalhães
authors.affiliation: a Faculty of Health Sciences, University of Brasília , Brasília , Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Lofrano-Porto
authors.affiliation: b Faculty of Dentistry, University of Campinas , Piracicaba , São Paulo , Brazil.
authors.forename: Ricardo D
authors.initials: RD
authors.lastname: Coletta
authors.affiliation: a Faculty of Health Sciences, University of Brasília , Brasília , Brazil.
authors.forename: Francisco A R
authors.initials: FA
authors.lastname: Neves
authors.affiliation: a Faculty of Health Sciences, University of Brasília , Brasília , Brazil.
authors.forename: Eliete N S
authors.initials: EN
authors.lastname: Guerra
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003603:Cytotoxins / Q000737:chemistry / Q000494:pharmacology; D030921:Erythroxylaceae / Q000737:chemistry*; D059585:G1 Phase Cell Cycle Checkpoints; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D014315:Triterpenes / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D018797:Cell Cycle Proteins; D003603:Cytotoxins; D010936:Plant Extracts; D014315:Triterpenes
keywords: Erythroxylum daphnites; apoptosis; cell cycle; cerrado biome; cytotoxicity; oral squamous cell carcinoma; triterpenes