Open Access Research article

Gallotannin-rich Caesalpinia spinosa fraction decreases the primary tumor and factors associated with poor prognosis in a murine breast cancer model

Claudia Urueña1, Juan Mancipe1, John Hernandez1, Diana Castañeda1, Luis Pombo2, Alejandra Gomez1, Alexzander Asea3 and Susana Fiorentino1*

Author Affiliations

1 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

2 Grupo de Farmacología Vegetal, Fundación Universitaria Juan N. Corpas, Carrera 111 #159 A 61, Bogotá, Colombia

3 Department of Microbiology, Biochemistry & Immunology, Morehouse School of Medicine, 720 Westview Avenue SW, Atlanta, GA, 30310, USA

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BMC Complementary and Alternative Medicine 2013, 13:74  doi:10.1186/1472-6882-13-74

Published: 3 April 2013

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.

Keywords:
Caesalpinia spinosa; Breast cancer; Apoptosis; 4T1; IL-6; Metastasis