Anticancer and Immunomodulatory Effects of Lactobacillus plantarum LS/07, Inulin and Melatonin in NMU-induced Rat Model of Breast Cancer.
OBJECTIVE
Chemopreventive activity of a new probiotic strain Lactobacillus plantarum LS/07 (PRO) and prebiotic oligofructose-enriched inulin (PRE) in rat mammary carcinogenesis induced by procarcinogen 7,12-dimethylbenz[a]anthracene has been reported before. This study evaluated the anticancer and immunomodulatory efficacy of PRO, PRE, PRO+PRE (PRO/PRE) and combination with melatonin (PRO+PRE+MEL) in a rat model, when breast cancer was induced by a direct-acting carcinogen N-nitroso-N-methylurea (NMU).


METHODS
Daily administration of PRO (at a dose of 8.4×10(8) colony-forming units (c.f.u.)/rat), PRE (in the diet, 20 g/kg) and MEL (in tap water, 20 mg/l) started 14 days before the first NMU dose and lasted for 16 weeks.


RESULTS
Although tumor growth was not altered, a marked decrease in the ratio of high-/low-grade carcinomas and in tumoral Ki-67 expression was found after PRO+PRE treatment; melatonin augmented these effects. PRO+PRE+MEL combination enhanced CD4(+) and CD8(+) T-cell tumor infiltration induced by PRO/PRE and increased CD25(+)FoxP3(+) regulatory T-cells in tumors.


CONCLUSIONS
In mammary carcinogenesis, Lactobacillus plantarum LS/07 and inulin exert prodifferentiating, antiproliferative and immunomodulatory activities, which are significantly amplified by melatonin co-administration.
Institute of Biology and Ecology, Faculty of Science, P.J. Šafárik University, Košice, Slovak Republic monika.kassayova@upjs.sk kruzliakpeter@gmail.com.
Monika
M
Kassayová
Department of Forensic Medicine, Faculty of Medicine, P.J. Šafárik University, Košice, Slovak Republic.
Nikita
N
Bobrov
Department of Experimental Medicine, Faculty of Medicine, P.J. Šafárik University, Košice, Slovak Republic.
Ladislav
L
Strojný
Institute of Biology and Ecology, Faculty of Science, P.J. Šafárik University, Košice, Slovak Republic.
Peter
P
Orendáš
Institute of Biology and Ecology, Faculty of Science, P.J. Šafárik University, Košice, Slovak Republic.
Vlasta
V
Demečková
Institute of Biology and Ecology, Faculty of Science, P.J. Šafárik University, Košice, Slovak Republic.
Rastislav
R
Jendželovský
Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovak Republic.
Peter
P
Kubatka
Institute of Biology and Ecology, Faculty of Science, P.J. Šafárik University, Košice, Slovak Republic.
Terézia
T
Kisková
Laboratory of Structural Biology and Proteomics, Central Laboratories, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Brno, Czech Republic monika.kassayova@upjs.sk kruzliakpeter@gmail.com.
Peter
P
Kružliak
Department of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovak Republic.
Marián
M
Adamkov
Department of Experimental Medicine, Faculty of Medicine, P.J. Šafárik University, Košice, Slovak Republic.
Alojz
A
Bomba
Institute of Biology and Ecology, Faculty of Science, P.J. Šafárik University, Košice, Slovak Republic.
Peter
P
Fedoročko
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D005260:Female; D007155:Immunologic Factors / Q000494:pharmacology*; D015850:Interleukin-6 / Q000502:physiology; D007444:Inulin / Q000494:pharmacology*; D048191:Lactiplantibacillus plantarum; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D008550:Melatonin / Q000494:pharmacology*; D008770:Methylnitrosourea; D019936:Probiotics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000502:physiology
D000970:Antineoplastic Agents; D007155:Immunologic Factors; D015850:Interleukin-6; D053773:Transforming Growth Factor beta1; D008770:Methylnitrosourea; D007444:Inulin; D008550:Melatonin
Breast cancer; Lactobacillus plantarum; N-nitroso-N-methylurea; melatonin; oligofructose-enriched inulin; prebiotic; probiotic