TY - JOUR
T1 - The dialyzable leukocyte extract TransferonTM inhibits tumor growth and brain metastasis in a murine model of prostate cancer
AU - Hernández-Esquivel, Miguel A.
AU - Pérez-Torres, Armando
AU - Romero-Romero, Laura
AU - Reyes-Matute, Alonso
AU - Loaiza, Brenda
AU - Mellado-Sánchez, Gabriela
AU - Pavón, Lenin
AU - Medina-Rivero, Emilio
AU - Pestell, Richard G.
AU - Pérez-Tapia, Sonia M.
AU - Velasco-Velázquez, Marco A.
N1 - Publisher Copyright:
© 2018 The Authors
PY - 2018/5
Y1 - 2018/5
N2 - Prostate cancer (PCa) is the second most frequently diagnosed cancer in men worldwide. Dialyzed Leukocyte Extracts (DLEs) are heterogeneous mixtures of low-molecular-weight peptides that improve clinical responses in various diseases. Here, we analyzed the effects of TransferonTM, a commercial DLE with characterized active pharmaceutical ingredient and proven batch-to-batch reproducibility, in preclinical models of PCa. We employed v-Src-transformed murine prostate epithelial (PEC-Src) cells, which recapitulate the transcriptional profiles in human PCa, can be grown in immunocompetent mice, and consistently form bone and brain metastases. In vitro, TransferonTM did not induce cytotoxicity nor alterations in migration /invasion of PEC-Src cells. In vivo, TransferonTM reduced metastatic dissemination after intracardiac injection of PEC-Src and inhibited tumor growth of subcutaneous isotransplants. The antineoplastic effect of TransferonTM correlated with changes in tumor infiltration, increased serum concentrations of IL-12 and CXCL1, and reduced levels of VEGF. Our results suggest that the antineoplastic effect produced by TransferonTM is due to its immunomodulatory activity and not by a direct effect on cancer cells, and indicate that TransferonTM could be beneficial as adjuvant therapy in PCa patients.
AB - Prostate cancer (PCa) is the second most frequently diagnosed cancer in men worldwide. Dialyzed Leukocyte Extracts (DLEs) are heterogeneous mixtures of low-molecular-weight peptides that improve clinical responses in various diseases. Here, we analyzed the effects of TransferonTM, a commercial DLE with characterized active pharmaceutical ingredient and proven batch-to-batch reproducibility, in preclinical models of PCa. We employed v-Src-transformed murine prostate epithelial (PEC-Src) cells, which recapitulate the transcriptional profiles in human PCa, can be grown in immunocompetent mice, and consistently form bone and brain metastases. In vitro, TransferonTM did not induce cytotoxicity nor alterations in migration /invasion of PEC-Src cells. In vivo, TransferonTM reduced metastatic dissemination after intracardiac injection of PEC-Src and inhibited tumor growth of subcutaneous isotransplants. The antineoplastic effect of TransferonTM correlated with changes in tumor infiltration, increased serum concentrations of IL-12 and CXCL1, and reduced levels of VEGF. Our results suggest that the antineoplastic effect produced by TransferonTM is due to its immunomodulatory activity and not by a direct effect on cancer cells, and indicate that TransferonTM could be beneficial as adjuvant therapy in PCa patients.
KW - Dialyzable leukocyte extract
KW - IL-12
KW - Metastasis
KW - Prostate cancer
KW - Transferon
KW - VEGF
UR - http://www.scopus.com/inward/record.url?scp=85043484861&partnerID=8YFLogxK
U2 - 10.1016/j.biopha.2018.03.012
DO - 10.1016/j.biopha.2018.03.012
M3 - Artículo
C2 - 29635903
SN - 0753-3322
VL - 101
SP - 938
EP - 944
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
ER -