title: Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.
abstract: Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9) CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9) CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain.
authors: Department of Molecular Biology and Genetics, School of Health Sciences, Democritus University of Thrace, University Campus-Dragana, 68100 Alexandroupolis, Greece.
authors: Angeliki
authors: A
authors: Tiptiri-Kourpeti
authors: Department of Molecular Biology and Genetics, School of Health Sciences, Democritus University of Thrace, University Campus-Dragana, 68100 Alexandroupolis, Greece.
authors: Katerina
authors: K
authors: Spyridopoulou
authors: Department of Molecular Biology and Genetics, School of Health Sciences, Democritus University of Thrace, University Campus-Dragana, 68100 Alexandroupolis, Greece.
authors: Valentina
authors: V
authors: Santarmaki
authors: Department of Molecular Biology and Genetics, School of Health Sciences, Democritus University of Thrace, University Campus-Dragana, 68100 Alexandroupolis, Greece.
authors: Georgios
authors: G
authors: Aindelis
authors: Department of Molecular Biology and Genetics, School of Health Sciences, Democritus University of Thrace, University Campus-Dragana, 68100 Alexandroupolis, Greece.
authors: Evgenia
authors: E
authors: Tompoulidou
authors: Department of Hematology, School of Health Sciences, Democritus University of Thrace, University Campus-Dragana, 68100 Alexandroupolis, Greece.
authors: Eleftheria E
authors: EE
authors: Lamprianidou
authors: Department of Molecular Biology and Genetics, School of Health Sciences, Democritus University of Thrace, University Campus-Dragana, 68100 Alexandroupolis, Greece.
authors: Georgia
authors: G
authors: Saxami
authors: Laboratory of Experimental Surgery & Surgical Research, School of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
authors: Petros
authors: P
authors: Ypsilantis
authors: Department of Pathology, Medical School, University of Ioannina, Ioannina, Greece.
authors: Evangeli S
authors: ES
authors: Lampri
authors: Laboratory of Experimental Surgery & Surgical Research, School of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
authors: Constantinos
authors: C
authors: Simopoulos
authors: Department of Hematology, School of Health Sciences, Democritus University of Thrace, University Campus-Dragana, 68100 Alexandroupolis, Greece.
authors: Ioannis
authors: I
authors: Kotsianidis
authors: Department of Molecular Biology and Genetics, School of Health Sciences, Democritus University of Thrace, University Campus-Dragana, 68100 Alexandroupolis, Greece.
authors: Alex
authors: A
authors: Galanis
authors: Department of Molecular Biology and Genetics, School of Health Sciences, Democritus University of Thrace, University Campus-Dragana, 68100 Alexandroupolis, Greece.
authors: Yiannis
authors: Y
authors: Kourkoutas
authors: Department of Molecular Biology and Genetics, School of Health Sciences, Democritus University of Thrace, University Campus-Dragana, 68100 Alexandroupolis, Greece.
authors: Dimitra
authors: D
authors: Dimitrellou
authors: Department of Molecular Biology and Genetics, School of Health Sciences, Democritus University of Thrace, University Campus-Dragana, 68100 Alexandroupolis, Greece.
authors: Katerina
authors: K
authors: Chlichlia
mesh_terms: D000818:Animals; D017209:Apoptosis; D001422:Bacterial Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D007780:Lacticaseibacillus casei / Q000502:physiology*; D051379:Mice; D019936:Probiotics; D000077022:Survivin; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D053221:TNF-Related Apoptosis-Inducing Ligand; D019938:Cyclin D1