title: Design and validation of an orally administrated active L. fermentum-L. acidophilus probiotic formulation using colorectal cancer ApcMin/+mouse model.
abstract: Probiotics have been shown to have beneficial properties in attenuating the risk of colorectal cancer (CRC) development. However, functional evidence to support such effects for some probiotic bacteria are relatively unknown. Here, we document a significant antioxidant, anti-proliferative and pro-apoptotic activities of Lactobacillus acidophilus ATCC 314 and Lactobacillus fermentum NCIMB 5221 on CRC cells, particularly when used in combination (La-Lf). Furthermore, a superior synergistic activity on the inhibition of tumor growth and modulation of cell proliferation and epithelial markers in the ApcMin/+CRC mouse model was explored, based on the expression levels of Ki-67, E-cadherin, β-catenin, and cleaved caspase-3 (CC3) proteins. The anti-cancer activity of La-Lf co-culture was significantly enhanced in vitro with significant reduced proliferation (38.8 ± 6.9 %, P = 0.009) and increased apoptosis (413 RUL, P < 0.001) towards cancer cells, as well as significant protection of normal colon cell growth from toxic treatment (18.6 ± 9.8 %, P = 0.001). La-Lf formulation (1010cfu/animal/day) altered aspects of intestinal tumorigenesis by significantly reducing intestinal tumor multiplicity (1.7-fold, P = 0.016) and downregulating cellular proliferation markers, including β-catenin (P = 0.041) and Ki-67 (P = 0.008). In conclusion, La-Lf showed greater protection against intestinal tumorigenesis supporting a potential use as a biotherapeutic for the prevention of CRC.
authors.affiliation: Department of Experimental Medicine, Faculty of Medicine, McGill University, 1110 Pine Avenue West, Montreal, QC, H3A 1A3, Canada.|Department of Biomedical Engineering, Faculty of Medicine, Biomedical Technology and Cell Therapy Research Laboratory, McGill University, 3775 University Street, Montreal, QC, H3A 2B4, Canada.|Lady Davis Institute for Medical Research and Segal Cancer Centre, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Côte-Ste-Catherine Road, Montreal, QC, H3T 1E2, Canada.
authors.forename: Imen
authors.initials: I
authors.lastname: Kahouli
authors.affiliation: Department of Biomedical Engineering, Faculty of Medicine, Biomedical Technology and Cell Therapy Research Laboratory, McGill University, 3775 University Street, Montreal, QC, H3A 2B4, Canada.|Department of Microbiology, Immunology and Infectious Diseases, CHU St. Justine Research Center, University of Montreal, 3175 Cote-Ste-Catherine, Montréal, QC, H3T 1C5, Canada.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Malhotra
authors.affiliation: Department of Biomedical Engineering, Faculty of Medicine, Biomedical Technology and Cell Therapy Research Laboratory, McGill University, 3775 University Street, Montreal, QC, H3A 2B4, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Westfall
authors.affiliation: Lady Davis Institute for Medical Research and Segal Cancer Centre, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Côte-Ste-Catherine Road, Montreal, QC, H3T 1E2, Canada.|Departments of Medicine and Oncology, Faculty of Medicine, Gerald Bronfman Centre, McGill University, Room 210, 546 Pine Avenue West, Montreal, QC, H2W 1S6, Canada.
authors.forename: Moulay A
authors.initials: MA
authors.lastname: Alaoui-Jamali
authors.affiliation: Department of Experimental Medicine, Faculty of Medicine, McGill University, 1110 Pine Avenue West, Montreal, QC, H3A 1A3, Canada. satya.prakash@mcgill.ca.|Department of Biomedical Engineering, Faculty of Medicine, Biomedical Technology and Cell Therapy Research Laboratory, McGill University, 3775 University Street, Montreal, QC, H3A 2B4, Canada. satya.prakash@mcgill.ca.
authors.forename: Satya
authors.initials: S
authors.lastname: Prakash
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells; D015820:Cadherins / Q000096:biosynthesis; D063646:Carcinogenesis / Q000187:drug effects*; D053148:Caspase 3 / Q000096:biosynthesis; D002457:Cell Extracts / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000517:prevention & control* / Q000628:therapy; D004195:Disease Models, Animal; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D007779:Lactobacillus acidophilus / Q000378:metabolism*; D052197:Limosilactobacillus fermentum / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019936:Probiotics / Q000627:therapeutic use*; D051176:beta Catenin / Q000096:biosynthesis
chemical_list: D000975:Antioxidants; D015820:Cadherins; D002457:Cell Extracts; D019394:Ki-67 Antigen; D051176:beta Catenin; D053148:Caspase 3
keywords: Apoptosis; Colorectal cancer; L. acidophilus; L. fermentum; Probiotics; Proliferation