title: Antimutagenicity and induction of antioxidant defense by flavonoid rich extract of Myrcia bella Cambess. in normal and tumor gastric cells.
abstract: BACKGROUND
  The Brazilian "Cerrado" is an important source of natural products, such as Myrcia bella Cambess (MB, also known as "mercurinho"). MB leaves are popularly used for the treatment of diabetes and gastrointestinal disorders; however, only its hypoglycemic activity has been experimentally described.
  
  
  OBJECTIVE
  Because MB is used to treat gastrointestinal disorders, the present study characterized biological activities of hydroalcoholic MB extract in human normal and tumor gastric cells.
  
  
  METHODS
  Cytotoxic, antiproliferative, genotoxic and protective effects were evaluated, as well as the effects of the MB extract on gene expression.
  
  
  RESULTS
  The MB extract induced cytotoxicity in tumor cells at lower concentrations compared with normal cells as assessed by the MTT assay. Moreover, the MB extract induced necrosis based on acridine orange/ethidium bromide staining. An antiproliferative effect was evidenced through an arrest in the G2/M phase detected by flow cytometry and a decrease in the nuclear division index using the cytokinesis-block micronucleus cytome assay. Cells treated with MB extract combined with doxorubicin (DXR) showed increased NUBDs, which may be related to the gene amplification of CCND1. Antimutagenic effects were also observed and may be associated with the antioxidant activities detected using the CM-H2DCFDA probe.
  
  
  CONCLUSIONS
  Our findings showed the following: (a) high concentrations of MB induced cytotoxicity and cell death by necrosis; (b) its antiproliferative effect was associated with G2/M arrest; and (c) its antioxidant activity could be responsible for the observed antimutagenic effects and for protective effects against gastrointestinal disorders previously described to MB. Although these effects are not specific to normal or tumor cells, they provide a panel of biological activities for further exploration.
authors.affiliation: Department of Biological Sciences, Faculty of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14801-902, Brazil. Electronic address: julianaserpeloni@yahoo.com.br.
authors.forename: Juliana Mara
authors.initials: JM
authors.lastname: Serpeloni
authors.affiliation: Department of General Biology, Center of Biological Sciences, State University of Londrina (UEL), Londrina 86057-970, Brazil.
authors.forename: Ana Flávia Leal
authors.initials: AF
authors.lastname: Specian
authors.affiliation: Department of General Biology, Center of Biological Sciences, State University of Londrina (UEL), Londrina 86057-970, Brazil.
authors.forename: Diego Luis
authors.initials: DL
authors.lastname: Ribeiro
authors.affiliation: Department of General Biology, Center of Biological Sciences, State University of Londrina (UEL), Londrina 86057-970, Brazil.
authors.forename: Katiuska
authors.initials: K
authors.lastname: Tuttis
authors.affiliation: Experimental Campus of São Vicente, São Paulo State University (UNESP), São Vicente 11350-000, Brazil.
authors.forename: Wagner
authors.initials: W
authors.lastname: Vilegas
authors.affiliation: Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, Uruguay.
authors.forename: Wilner
authors.initials: W
authors.lastname: Martínez-López
authors.affiliation: Department of Biological Sciences, Faculty of Sciences, São Paulo State University (UNESP), Bauru 17033-360, Brazil.
authors.forename: Anne Lígia
authors.initials: AL
authors.lastname: Dokkedal
authors.affiliation: Department of Biological Sciences, Faculty of Sciences, São Paulo State University (UNESP), Bauru 17033-360, Brazil; Department of Botany, Institute of Bioscience, São Paulo State University (UNESP), Botucatu 18618-970, Brazil.
authors.forename: Luiz Leonardo
authors.initials: LL
authors.lastname: Saldanha
authors.affiliation: Department of General Biology, Center of Biological Sciences, State University of Londrina (UEL), Londrina 86057-970, Brazil.
authors.forename: Ilce Mara de Syllos
authors.initials: IM
authors.lastname: Cólus
authors.affiliation: Department of Biological Sciences, Faculty of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14801-902, Brazil.
authors.forename: Eliana Aparecida
authors.initials: EA
authors.lastname: Varanda
mesh_terms: D016587:Antimutagenic Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000633:toxicity; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000235:genetics; D004247:DNA / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D048629:Micronuclei, Chromosome-Defective; D027822:Myrtaceae; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves; D013270:Stomach / Q000166:cytology*
chemical_list: D016587:Antimutagenic Agents; D000970:Antineoplastic Agents; D000975:Antioxidants; C530104:CCND1 protein, human; D005419:Flavonoids; D010936:Plant Extracts; D019938:Cyclin D1; D004317:Doxorubicin; D004247:DNA
keywords: Acridine orange (PubChem CID: 62344); Antioxidant; Antiproliferative; Azure A (PubChem CID: 13735); Bromophenol blue (PubChem CID: 8272); Cytochalasin B (PubChem CID: 5311281); Dimethyl sulfoxide (PubChem CID: 679); Doxorubicin (PubChem CID: 31703); Ethidium bromide (PubChem CID: 14710); Gastric disorders; Hydrogen peroxide (PubChem CID: 784); Mutagenicity; Myrcia bella; Necrosis; Propidium iodide (PubChem CID: 104981); Thiazolyl blue (PubChem CID: 64965)