title: Gallotannin-rich Caesalpinia spinosa fraction decreases the primary tumor and factors associated with poor prognosis in a murine breast cancer model.
abstract: BACKGROUND
  Several treatment alternatives are available for primary breast cancer, although those for metastatic disease or inflammation associated with tumor progression are ineffective. Therefore, there is a great need for new therapeutic alternatives capable of generating an immune response against residual tumor cells, thus contributing to eradication of micrometastases and cancer stem cells. The use of complex natural products is an excellent therapeutic alternative widely used by Chinese, Hindu, Egyptian, and ancestral Latin-American Indian populations.
  
  
  METHODS
  The present study evaluated cytotoxic, antitumor, and tumor progression activities of a gallotannin-rich fraction derived from Caesalpinia spinosa (P2Et). The parameters evaluated in vitro were mitochondrial membrane depolarization, phosphatidylserine externalization, caspase 3 activation, DNA fragmentation, and clonogenic activity. The parameters evaluated in vivo were tumor growth, leukocyte number, metastatic cell number, and cytokine production by flow cytometry.
  
  
  RESULTS
  The in vitro results showed that the P2Et fraction induced apoptosis with mitochondrial membrane potential loss, phosphatidylserine externalization, caspase 3 activation, DNA fragmentation, and decreased clonogenic capacity of 4T1 cells. In vivo, the P2Et fraction induced primary tumor reduction in terms of diameter and weight in BALB/c mice transplanted with 4T1 cells and decreased numbers of metastatic cells, mainly in the spleen. Furthermore, decreases in the number of peripheral blood leukocytes (leukemoid reaction) and interleukin 6 (IL-6) serum levels were found, which are events associated with a poor prognosis. The P2Et fraction exerts its activity on the primary tumor, reduces cell migration to distant organs, and decreases IL-6 serum levels, implying tumor microenvironment mechanisms.
  
  
  CONCLUSIONS
  Overall, the P2Et fraction lessens risk factors associated with tumor progression and diminishes primary tumor size, showing good potential for use as an adjuvant in breast cancer ER(+) treatment.
authors.affiliation: Grupo de Inmunobiología y Biología Celular, Departamento de Microbiología, Facultad de Ciencias, Pontificia Universidad Javeriana, Carrera 7 N, 43-82 Building 52, Office 608, Bogotá, Colombia.
authors.forename: Claudia
authors.initials: C
authors.lastname: Urueña
authors.forename: Juan
authors.initials: J
authors.lastname: Mancipe
authors.forename: John
authors.initials: J
authors.lastname: Hernandez
authors.forename: Diana
authors.initials: D
authors.lastname: Castañeda
authors.forename: Luis
authors.initials: L
authors.lastname: Pombo
authors.forename: Alejandra
authors.initials: A
authors.lastname: Gomez
authors.forename: Alexzander
authors.initials: A
authors.lastname: Asea
authors.forename: Susana
authors.initials: S
authors.lastname: Fiorentino
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D029911:Caesalpinia / Q000737:chemistry*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D047348:Hydrolyzable Tannins / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000008:administration & dosage*; D011379:Prognosis
chemical_list: D047348:Hydrolyzable Tannins; D015850:Interleukin-6; D010936:Plant Extracts
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