Anticancer and Immunomodulatory Effects of Lactobacillus plantarum LS/07, Inulin and Melatonin in NMU-induced Rat Model of Breast Cancer

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). 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. 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. In mammary carcinogenesis, Lactobacillus plantarum LS/07 and inulin exert prodifferentiating, antiproliferative and immunomodulatory activities, which are significantly amplified by melatonin co-administration.