Antitumor effect of the combination of manumycin A and Immodin is associated with antiplatelet activity and increased granulocyte tumor infiltration in a 4T1 breast tumor model

Solár,Peter; Sačková,Veronika; Hrčková,Gabriela; Demečková,Vlasta; Kassayová,Monika; Bojková,Bianka; Mudroňová,Dagmar; Gancarčíková,Soňa; Jendželovský,Rastislav; Fedoročko,Peter

doi:10.3892/or.2016.5265

Antitumor effect of the combination of manumycin A and Immodin is associated with antiplatelet activity and increased granulocyte tumor infiltration in a 4T1 breast tumor model

Authors:
- Peter Solár
- Veronika Sačková
- Gabriela Hrčková
- Vlasta Demečková
- Monika Kassayová
- Bianka Bojková
- Dagmar Mudroňová
- Soňa Gancarčíková
- Rastislav Jendželovský
- Peter Fedoročko
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Affiliations: Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Šafárik University in Košice, 041 54 Košice, Slovak Republic, Institute of Parasitology of Slovak Academy of Science, 040 01 Košice, Slovak Republic, University of Veterinary Medicine and Pharmacy, 041 81 Košice, Slovak Republic
Published online on: November 22, 2016 https://doi.org/10.3892/or.2016.5265
Pages: 368-378

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Abstract

Manumycin A is a natural antibiotic isolated from Streptomyces parvulus with broad range of biological activities including antineoplastic activity in several in vitro and in vivo cancer models. Immodin [dialyzable leukocyte extract (DLE)] is a dialysate released from disintegrated blood leukocytes of healthy donors which exerts immunonormalizing effects on cell-mediated immune responses. The aim of the present study was to explore the antitumor potential of the combination of manumycin A and Immodin in an experimental breast cancer model. Experiments were carried using a 4T1 tumor-bearing BALB/c mouse model. Survival analysis, tumor growth, hematological and biochemical profiles, leukocyte differential, phagocytic activity of leukocytes and histology of the primary tumor were examined. The combination treatment suppressed the tumor growth and prolonged the survival of tumor-bearing mice, decreased the number of monocytes, plateletes and plateletcrit in peripheral blood of the tumor-bearing mice and increased the infiltration of neutrophils and eosinophils in the primary tumor. Moreover, individual therapies enhanced the phagocytic activity of monocytes and neutrophils. These findings demonstrate the antitumor effect of the combination of manumycin A and Immodin in 4T1 tumor-bearing mice associated with strong antiplatelet activity and innate immunity activation.

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