title: Sesquiterpene lactones of Moquiniastrum polymorphum subsp. floccosum have antineoplastic effects in Walker-256 tumor-bearing rats.
abstract: OBJECTIVE
  This study aimed to evaluate the in vivo antitumor actions and toxicity of the dichloromethane fraction (F1B) of Moquiniastrum polymorphum subsp. floccosum (formerly Gochnatia polymorpha ssp. floccosa), composed of sesquiterpene lactones, against Walker-256 carcinosarcoma in rats.
  
  
  METHODS
  Male Wistar rats received 100 mg kg(-1) F1B per day orally for 16 days after subcutaneous inoculation of Walker-256 cells in the pelvic limb. The tumor progression was monitored, and after treatment, tumor weight, oxidative stress, plasma biochemistry, inflammatory parameters, gene expression and histology of tumor and/or liver were evaluated. The toxicity of F1B was analyzed through the relative weight of organs. Additionally, an LD50 test was performed in mice.
  
  
  RESULTS
  F1B treatment significantly reduced tumor volume and weight. There was no difference in oxidative stress in tumor tissue after treatment. F1B treatment modified hepatic glutathione and superoxide dismutase, and normalized plasma glucose, alkaline phosphatase, and amylase. F1B did not affect the activity of myeloperoxidase and N-acetylglucosaminidase or the nitric oxide levels in tumor tissue. However, F1B decreased the tumor necrosis factor (TNF)-α levels. Additionally, F1B increased apoptosis in the tumor, mediated by up-regulation of the p53 and Bax gene expression. No clinical signs of toxicity or death were observed in the rats treated with F1B. The LD50 calculated for mice was 1209 mg kg(-1).
  
  
  CONCLUSIONS
  F1B, which is rich in sesquiterpene lactones, showed antitumor activity against Walker-256 carcinosarcoma. This effect may be, at least in part, related to the induction of apoptosis and inhibition of TNF-α signaling.
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Gracianny Gomes
authors.initials: GG
authors.lastname: Martins
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Francislaine Aparecida dos Reis
authors.initials: FA
authors.lastname: Lívero
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Aline Maria
authors.initials: AM
authors.lastname: Stolf
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Caroline Machado
authors.initials: CM
authors.lastname: Kopruszinski
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Cibele Campos
authors.initials: CC
authors.lastname: Cardoso
authors.affiliation: Department of Veterinary Medicine, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Olair Carlos
authors.initials: OC
authors.lastname: Beltrame
authors.affiliation: Department of Medical Pathology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: José Ederaldo
authors.initials: JE
authors.lastname: Queiroz-Telles
authors.affiliation: Department of Chemistry, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Regiane Lauriano Batista
authors.initials: RL
authors.lastname: Strapasson
authors.affiliation: Department of Chemistry, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Maria Élida Alves
authors.initials: MÉ
authors.lastname: Stefanello
authors.affiliation: Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: Oude-Elferink
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil. Electronic address: aleacco@ufpr.br.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Acco
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use*; D019659:Asteraceae / Q000737:chemistry*; D002279:Carcinoma 256, Walker / Q000188:drug therapy* / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008968:Molecular Conformation; D024301:Plant Bark / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007783:Lactones; D012717:Sesquiterpenes
keywords: Acute toxicity (LD(50)); Cambará; Cancer; Gochnatia polymorpha ssp. floccosa; Moquiniastrum polymorphum subsp. floccosum; Walker-256 tumor