title: 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.
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.
authors.affiliation: Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Šafárik University in Košice, 041 54 Košice, Slovak Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Solár
authors.affiliation: Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Šafárik University in Košice, 041 54 Košice, Slovak Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Sačková
authors.affiliation: Institute of Parasitology of Slovak Academy of Science, 040 01 Košice, Slovak Republic.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Hrčková
authors.affiliation: Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Šafárik University in Košice, 041 54 Košice, Slovak Republic.
authors.forename: Vlasta
authors.initials: V
authors.lastname: Demečková
authors.affiliation: Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Šafárik University in Košice, 041 54 Košice, Slovak Republic.
authors.forename: Monika
authors.initials: M
authors.lastname: Kassayová
authors.affiliation: Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Šafárik University in Košice, 041 54 Košice, Slovak Republic.
authors.forename: Bianka
authors.initials: B
authors.lastname: Bojková
authors.affiliation: University of Veterinary Medicine and Pharmacy, 041 81 Košice, Slovak Republic.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Mudroňová
authors.affiliation: University of Veterinary Medicine and Pharmacy, 041 81 Košice, Slovak Republic.
authors.forename: Soňa
authors.initials: S
authors.lastname: Gancarčíková
authors.affiliation: Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Šafárik University in Košice, 041 54 Košice, Slovak Republic.
authors.forename: Rastislav
authors.initials: R
authors.lastname: Jendželovský
authors.affiliation: Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Šafárik University in Košice, 041 54 Košice, Slovak Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Fedoročko
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D005260:Female; D006098:Granulocytes / Q000187:drug effects / Q000473:pathology; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology; D007958:Leukocyte Count; D007962:Leukocytes / Q000737:chemistry*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008807:Mice, Inbred BALB C; D010587:Phagocytosis / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D011090:Polyenes / Q000008:administration & dosage; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage; D016019:Survival Analysis
chemical_list: D007155:Immunologic Factors; D010975:Platelet Aggregation Inhibitors; D011090:Polyenes; D053284:Polyunsaturated Alkamides; C054474:manumycin