title: Kefir exhibits anti‑proliferative and pro‑apoptotic effects on colon adenocarcinoma cells with no significant effects on cell migration and invasion.
abstract: Kefir, a fermented milk product, exhibits anti‑tumoral activity in vivo; yet its mechanism of action remains elusive. Recent studies have focused on the mechanism of action of kefir on cancer cells in vitro. The current study aims at examining the effect of kefir on cell survival, proliferation, and motility of colorectal cancer (CRC) cells. Kefir's anti‑cancer potential was tested on CRC cell lines, Caco‑2 and HT‑29, through cytotoxicity, proliferation, and apoptotic assays. The expression of certain genes involved in proliferation and apoptosis was measured using reverse transcriptase‑polymerase chain reaction (RT‑PCR) and western blotting. To assess the effect of kefir on cancer metastasis, wound‑healing and time‑lapse movies, in addition to collagen‑based invasion assay, were used. The results show that cell‑free fractions of kefir exhibit an anti‑proliferative effect on Caco‑2 and HT‑29 cells. Analysis of DNA content by flow cytometry revealed the ability of kefir to induce cell cycle arrest at the G1 phase. Kefir was also found to induce apoptosis, as seen by cell death ELISA. Results from RT‑PCR showed that kefir decreases the expression of transforming growth factor α (TGF‑α); and transforming growth factor‑β1 (TGF‑β1) in HT‑29 cells. Western blotting results revealed an upregulation in Bax:Bcl‑2 ratio, confirming the pro‑apoptotic effect of kefir, and an increase in p53 independent‑p21 expression upon kefir treatment. MMP expression was not altered by kefir treatment. Furthermore, results from time‑lapse motility movies, wound‑healing, and invasion assays showed no effect on the motility of colorectal as well as breast (MCF‑7 and MB‑MDA‑231) cancer cells upon kefir treatment. Our data suggest that kefir is able to inhibit the proliferation and induce apoptosis in HT‑29 and Caco‑2 CRC cells, yet it does not exhibit a significant effect on the motility and invasion of these cells in vitro.
authors.affiliation: Department of Natural Sciences, Lebanese American University, Beirut 1102 2801, Lebanon.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Khoury
authors.affiliation: Department of Natural Sciences, Lebanese American University, Beirut 1102 2801, Lebanon.
authors.forename: Stephany
authors.initials: S
authors.lastname: El-Hayek
authors.affiliation: Department of Natural Sciences, Lebanese American University, Beirut 1102 2801, Lebanon.
authors.forename: Omayr
authors.initials: O
authors.lastname: Tarras
authors.affiliation: Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon.
authors.forename: Marwan
authors.initials: M
authors.lastname: El-Sabban
authors.affiliation: Department of Natural Sciences, Lebanese American University, Beirut 1102 2801, Lebanon.
authors.forename: Mirvat
authors.initials: M
authors.lastname: El-Sibai
authors.affiliation: Department of Natural Sciences, Lebanese American University, Beirut 1102 2801, Lebanon.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rizk
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D043302:Cultured Milk Products; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis
chemical_list: D009363:Neoplasm Proteins