Abstract
BackgroundSeveral 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.MethodsThe 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.ResultsThe 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.ConclusionsOverall, 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.
Highlights
Several treatment alternatives are available for primary breast cancer, those for metastatic disease or inflammation associated with tumor progression are ineffective
P2Et fraction is cytotoxic to 4T1 tumor cells in vitro The cytotoxicity of P2Et fraction on 4T1 cells was evaluated by methylthiazol tetrazolium (MTT) assay
We evaluated the secretion of interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), IL-10, IFNγ, IL-12p70, and TNF-α by 4T1 cells after treatment with P2Et fraction, doxorubicin, or ethanol for 6, 12, 24, and 48 h
Summary
Several treatment alternatives are available for primary breast cancer, those for metastatic disease or inflammation associated with tumor progression are ineffective. There are several therapeutic alternatives for breast cancer, including surgery, hormone therapy, chemotherapy, and radiotherapy These therapies are ineffective for metastatic disease [3]. The use of complex natural products is an excellent therapeutic alternative widely used by Chinese, Hindu, Egyptian, and ancestral Latin-American Indian populations [5]. Active compounds, such as hydrolyzable or condensed tannins [6], have high therapeutic potential in cancer treatment. Green tea-derived condensed tannins, for example, have been extensively studied Their activities include tumor growth inhibition, decreased cell proliferation, increased apoptosis, and angiogenic suppression [7]. A gallotanninrich fruit extract from Terminalia chebula induces apoptosis in the murine and human breast cancer cells S115 and MCF-7, respectively [9]
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