Kefir exhibits anti-proliferative and pro-apoptotic effects on colon adenocarcinoma cells with no significant effects on cell migration and invasion (647.24)

Abstract

Background: Previous studies showed that kefir, a fermented milk product, exhibited 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. Methods: 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 assessed using RT-PCR and western blot analysis to determine the possible mechanism of action of kefir. To assess the effect of kefir on cancer metastasis, wound healing and time-lapse movies, in addition to collagen-based invasion assay, were used. Results: Results have shown 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 TGF-α and TGF-β1 in HT-29 cells. Western blot 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. Conclusion: 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. Keywords: Kefir, Colorectal Cancer, Apoptosis, Cell Motility, Cell Invasion.