title: Anticancer activity of flavonol and flavan-3-ol rich extracts from Croton celtidifolius latex.
abstract: BACKGROUND
  Croton celtidifolius Baill (Euphorbiaceae) is a tree found in the Atlantic Forest in Southern Brazil, where it is commonly known as "Sangue-de-Dragão". Its red latex is used traditionally for treating ulcers, diabetes and cancer.
  
  
  OBJECTIVE
  To evaluate antitumor activities of Croton celtififolius latex in vitro and in vivo.
  
  
  METHODS
  Phytochemical analyses were conducted using HPLC-DAD-MS. Cytotoxic, nuclease and pro-apoptotic properties were determined using the tetrazolium salt assay (MTT), plasmid DNA damage assay and ethidium bromide (EB)/acridine orange methods, respectively, and antitumor activity was determined in the Ehrlich ascites carcinoma (EAC) mouse model.
  
  
  RESULTS
  Phytochemical studies indicated a high phenol content of flavonols (45.67 ± 0.24 and 18.01 ± 0.23 mg/mL of myricetin and quercetin, respectively) and flavan-3-ols (114.12 ± 1.84 and 1527.41 ± 16.42 mg/L of epicatechin and epigallocatechin, respectively) in latex. These compounds reduced MCF-7 and EAC cell viability in the MTT assay (IC50 = 169.0 ± 1.8 and 187.0 ± 2.2 μg/mL, respectively). Latex compounds caused significant DNA fragmentation and increased the number of apoptotic cells (negative control (NC), 12%; latex, 41%) as indicated by differential staining in the EB/acridine orange assay. The in vivo latex treatment at 3.12 mg/kg/day reduced the body weight by 7.57 ± 2.04 g and increased median survival time to 17.5 days when compared to the NC group (13.0 days). In addition, the highest latex concentration inhibited tumor growth by 56%.
  
  
  CONCLUSIONS
  These results agree with ethno-pharmacological reports showing cytotoxicity and antitumor activity of C. celtidifolius latex. The mechanism of antitumor action may be related to direct DNA fragmentation that reduces survival and induces apoptosis.
authors.affiliation: Department of Biochemistry, Universidade Federal de Santa Catarina, Florianopolis, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Biscaro
authors.forename: Eduardo Benedetti
authors.initials: EB
authors.lastname: Parisotto
authors.forename: Vanilde Citadini
authors.initials: VC
authors.lastname: Zanette
authors.forename: Tania Mara Fischer
authors.initials: TM
authors.lastname: Günther
authors.forename: Eduardo Antonio
authors.initials: EA
authors.lastname: Ferreira
authors.forename: Eliana Fortes
authors.initials: EF
authors.lastname: Gris
authors.forename: João Francisco Gomes
authors.initials: JF
authors.lastname: Correia
authors.forename: Claus Tröger
authors.initials: CT
authors.lastname: Pich
authors.forename: Fulvio
authors.initials: F
authors.lastname: Mattivi
authors.forename: Danilo Wilhelm
authors.initials: DW
authors.lastname: Filho
authors.forename: Rozangela Curi
authors.initials: RC
authors.lastname: Pedrosa
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001938:Brazil; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D029802:Croton / Q000737:chemistry*; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D044948:Flavonols / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007840:Latex / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D061986:MCF-7 Cells; D008297:Male; D008519:Medicine, Traditional; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; D044948:Flavonols; D007840:Latex; D010936:Plant Extracts; C404987:flavan-3-ol