title: Preclinical anticancer effectiveness of a fraction from Casearia sylvestris and its component Casearin X: in vivo and ex vivo methods and microscopy examinations.
abstract: BACKGROUND
  Casearia sylvestris (Salicaceae) is found in South America and presents antiulcerogenic, cytotoxic, antimicrobial, anti-inflammatory and antihypertensive activities.
  
  
  OBJECTIVE
  To assess the in vivo and ex vivo antitumor action of a fraction with casearins (FC) and its main component - Casearin X-isolated from C. sylvestris leaves.
  
  
  METHODS
  Firstly, Sarcoma 180 bearing Swiss mice were treated with FC and Cas X for 7 days. Secondly, BALB/c nude animals received hollow fibers with colon carcinoma (HCT-116) or glioblastoma (SF-295) cells and were treated with FC for 4 days. On 5th day, proliferation was determined by MTT assay.
  
  
  RESULTS
  FC 10 and 25mg/kg/day i.p. and 50mg/kg/day oral and Cas X 25mg/kg/day i.p. and 50mg/kg/day oral revealed tumor growth inhibition rates of 35.8, 86.2, 53.7, 90.0 and 65.5% and such tumors demonstrated rare mitoses and coagulation necrosis areas. Similarly, FC reduced multiplying of HCT-116 and SF-295 cells when evaluated by the Hollow Fiber Assay (2.5 and 5mg/kg/day i.p. and 25 and 50mg/kg/day oral), with cell growth inhibition rates ranging from 33.3 to 67.4% (p<0.05). Flow cytometry experiments revealed that FC reduced membrane integrity and induced DNA fragmentation and mitochondrial depolarization (p<0.05).
  
  
  CONCLUSIONS
  FC and Cas X were efficient antitumor substances against murine and human cancer cells and caused reversible morphological changes in liver, kidneys and spleens, emphasizing clerodane diterpenes as an emerging class of anticancer molecules.
authors.affiliation: Laboratory in Experimental Cancerology, Department of Biophysics and Physiology, Federal University of Piauí, Teresina, Brazil; Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Brazil; Postgraduate Program in Biotechnology, Federal University of Piauí, Teresina, Brazil. Electronic address: pmpf@ufpi.edu.br.
authors.forename: Paulo Michel Pinheiro
authors.initials: PMP
authors.lastname: Ferreira
authors.affiliation: Oswaldo Cruz Foundation, Salvador, Brazil.
authors.forename: Daniel Pereira
authors.initials: DP
authors.lastname: Bezerra
authors.affiliation: Postgraduate Program in Biotechnology, Federal University of Piauí, Teresina, Brazil.
authors.forename: Jurandy do Nascimento
authors.initials: JDN
authors.lastname: Silva
authors.affiliation: Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Brazil; Department of Pharmacy, Federal University of Piauí, Teresina, Brazil.
authors.forename: Marcília Pinheiro
authors.initials: MP
authors.lastname: da Costa
authors.affiliation: Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Brazil.
authors.forename: José Roberto de Oliveira
authors.initials: JRO
authors.lastname: Ferreira
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Nylane Maria Nunes
authors.initials: NMN
authors.lastname: Alencar
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Ingrid Samantha Tavares de
authors.initials: IST
authors.lastname: Figueiredo
authors.affiliation: Chemistry Institute, State University of São Paulo, Araraquara, Brazil.
authors.forename: Alberto José
authors.initials: AJ
authors.lastname: Cavalheiro
authors.affiliation: Radioisotopes Research Laboratory, Center for Medical Nuclear, State University of São Paulo, São Paulo, Brazil.
authors.forename: Camila Maria Longo
authors.initials: CML
authors.lastname: Machado
authors.affiliation: Department of Radiology, Faculty of Medicine, State University of São Paulo, São Paulo, Brazil.
authors.forename: Roger
authors.initials: R
authors.lastname: Chammas
authors.affiliation: Department of Clinical Odontology, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Ana Paula Negreiros Nunes
authors.initials: APNN
authors.lastname: Alves
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Manoel Odorico de
authors.initials: MO
authors.lastname: Moraes
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil; Oswaldo Cruz Foundation, Fortaleza, Brazil.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pessoa
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D037821:Casearia; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045785:Diterpenes, Clerodane / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007958:Leukocyte Count; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008853:Microscopy; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves; D047368:Tumor Burden / Q000187:drug effects
chemical_list: C548433:1-(acetyloxy)-3,5,6,6a,7,8,9,10-octahydro-10-hydroxy-7,8-dimethyl-7-(3-methylpenta-2,4-dien-1-yl)naphtho(1,8a-c)furan-3,5-diyl dibutanoate; D000972:Antineoplastic Agents, Phytogenic; D045785:Diterpenes, Clerodane; D010936:Plant Extracts
keywords: Antineoplastic; Casearin X; Hollow fiber assay; Leukogram; Sarcoma 180; Toxicity