Arginine deiminase originating from Lactococcus lactis ssp lactis American Type Culture Collection (ATCC) 7962 induces G1-phase cell-cycle rrest and apoptosis in SNU-1 stomach adenocarcinoma cells

There are multiple lines of evidence thin facile acid bacteria (LAB) exert cancer-preventive effects However, the underlying mechanisms are poorly understood In the present study we found that the cytoplasmic fraction of Lactococcus lactus ssp latus American Type Culture Collection (ATCC) 7962 exerted the strongest antiproliferative effects (half-maximal inhibitory concentration (IC50) = 17 mu g/ml) in SNU-1 human stomach cancer cells and arginine derminase (ADI. EC 3 5.3 6) activity We also cloned, expressed and purified ADI from L lactus ssp lactus ATCC 7962 (LADI) Both purified ADI from L lactus (PADI, IC50 = 2 mu g/ml) and recombinant ADI originating from LAD[ (IC50 = 06 mu g/ml) inhibited the proliferation of SNU-1 cells. LADI induces G(0)/G(1)-phase arrest. sub-G, accumulation. DNA condensation and DNA fragmentation In SNU-1 cells 4'.6-diamidino-2-phenylindole (DAPI) staining and DNA fragmentation data provide evidence that LADI induces apoptosis in SNU-1 cells LADI increased the expressions of p53 and p27(Kip1), and decreased the expressions of cyclin D-1, c-myc and Bcl-xL in SNU-1 cells. However, LADI had no effects on the expressions of p21(Cip1) and Bcl-2. Collectively, these data indicate that ADI induces apoptosis and G(0)/G(1)-phase arrest of SNU-1 cells, which might contribute to the chemopreventive potential of LAB.