title: The Paraguayan Rhinella toad venom: Implications in the traditional medicine and proliferation of breast cancer cells.
abstract: BACKGROUND
  Toads belonging to genus Rhinella are used in Paraguayan traditional medicine to treat cancer and skin infections.
  
  
  OBJECTIVE
  The objective of the study was to determine the composition of venoms obtained from three different Paraguayan Rhinella species, to establish the constituents of a preparation sold in the capital city of Paraguay to treat cancer as containing the toad as ingredient, to establish the effect of the most active Rhinella schneideri venom on the cell cycle using human breast cancer cells and to assess the antiprotozoal activity of the venoms.
  
  
  METHODS
  The venom obtained from the toads parotid glands was analyzed by HPLC-MS-MS. The preparation sold in the capital city of Paraguay to treat cancer that is advertised as made using the toad was analyzed by HPLC-MS-MS. The effect of the R. schneideri venom and the preparation was investigated on human breast cancer cells. The antiprotozoal activity was evaluated on Leishmania braziliensis, L. infantum and murine macrophages.
  
  
  RESULTS
  From the venoms of R. ornata, R. schneideri and R. scitula, some 40 compounds were identified by spectroscopic and spectrometric means. Several minor constituents are reported for the first time. The preparation sold as made from the toad did not contained bufadienolides or compounds that can be associated with the toad but plant compounds, mainly phenolics and flavonoids. The venom showed activity on human breast cancer cells and modified the cell cycle proliferation. The antiprotozoal effect was higher for the R. schneideri venom and can be related to the composition and relative ratio of constituents compared with R. ornata and R. scitula.
  
  
  CONCLUSIONS
  The preparation sold in the capital city of Paraguay as containing the toad venom, used popularly to treat cancer did not contain the toad venom constituents. Consistent with this, this preparation was inactive on proliferation of human breast cancer cells. In contrast, the toad venoms of Rhinella species altered the cell cycle progression, affecting the proliferation of malignant cells. The findings suggest that care should be taken with the providers of the preparation and that the crude drug present a strong activity towards human breast cancer cell lines. The antiprotozoal effect of the R. schneideri venom was moderate while the venom of R. ornata was devoid of activity and that of R. scitula was active at very high concentration.
authors.affiliation: Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, 3460000 Talca, Chile. Electronic address: schmeda@utalca.cl.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Schmeda-Hirschmann
authors.affiliation: Centro para el Desarrollo de la Investigación Científica (CEDIC), Manduvira 635 entre 15 de Agosto y O` Leary, Barrio La Encarnación, Código Postal: 1255, Asunción, Paraguay.
authors.forename: Celeste Vega
authors.initials: CV
authors.lastname: Gomez
authors.affiliation: Centro para el Desarrollo de la Investigación Científica (CEDIC), Manduvira 635 entre 15 de Agosto y O` Leary, Barrio La Encarnación, Código Postal: 1255, Asunción, Paraguay.
authors.forename: Antonieta
authors.initials: A
authors.lastname: Rojas de Arias
authors.affiliation: Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, 3460000 Talca, Chile.
authors.forename: Alberto
authors.initials: A
authors.lastname: Burgos-Edwards
authors.affiliation: Centro para el Desarrollo de la Investigación Científica (CEDIC), Manduvira 635 entre 15 de Agosto y O` Leary, Barrio La Encarnación, Código Postal: 1255, Asunción, Paraguay.
authors.forename: Jorge
authors.initials: J
authors.lastname: Alfonso
authors.affiliation: Centro para el Desarrollo de la Investigación Científica (CEDIC), Manduvira 635 entre 15 de Agosto y O` Leary, Barrio La Encarnación, Código Postal: 1255, Asunción, Paraguay.
authors.forename: Miriam
authors.initials: M
authors.lastname: Rolon
authors.affiliation: Instituto de Investigación Biológica del Paraguay, CP 1429 Asunción, Paraguay.
authors.forename: Francisco
authors.initials: F
authors.lastname: Brusquetti
authors.affiliation: Instituto de Investigación Biológica del Paraguay, CP 1429 Asunción, Paraguay.
authors.forename: Flavia
authors.initials: F
authors.lastname: Netto
authors.affiliation: Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile and Geroscience Center for Brain Health and Metabolism, Independencia 1027, Casilla 7, Santiago, Chile.
authors.forename: Félix A
authors.initials: FA
authors.lastname: Urra
authors.affiliation: Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile and Geroscience Center for Brain Health and Metabolism, Independencia 1027, Casilla 7, Santiago, Chile.
authors.forename: César
authors.initials: C
authors.lastname: Cárdenas
mesh_terms: D000664:Amphibian Venoms / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D002024:Bufo marinus; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008519:Medicine, Traditional / Q000379:methods*; D051379:Mice; D010239:Paraguay
chemical_list: D000664:Amphibian Venoms
keywords: Antiproliferative activity; Antiprotozoal; Bufadienolide derivatives; Paraguayan toads; Rhinella ornata; Rhinella schneideri; Rhinella scitula