Lactococcus lactis ssp. lactis inhibits the proliferation of SNU-1 human stomach cancer cells through induction of G0/G1 cell cycle arrest and apoptosis via p53 and p21 expression

Ann N Y Acad Sci. 2009 Aug:1171:270-5. doi: 10.1111/j.1749-6632.2009.04721.x.


We investigated the antiproliferative effects of the cytoplasmic fraction of Lactococcus lactis ssp. lactis (L.lac CF) on the SNU-1 human stomach cancer cell line. The proliferation of SNU-1 cells was inhibited by treatment with L.lac CF in a time- and dose-dependent manner. L.lac CF caused G0/G1 cell cycle arrest, which was associated with an increase in p53 and p21 expression, the reduction of cyclin D1 expression, and retinoblastoma protein phosphorylation. L.lac CF induced apoptosis in SNU-1 cells, as demonstrated by increased nucleus condensation and a sub-G1 peak. Caspase-3 activation, the induction of p53, and the downregulation of Bcl-2 were also observed in L.lac CF-treated cells. Thus, the inhibitory effect of L.lac CF on SNU-1 cell growth is mainly attributable to the induction of G0/G1 cell cycle arrest and apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Biological Factors / chemistry
  • Biological Factors / pharmacology*
  • Blotting, Western
  • Caspase 3 / metabolism
  • Cell Cycle / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • G1 Phase / drug effects
  • Humans
  • Lactococcus lactis / chemistry*
  • Phosphorylation / drug effects
  • Resting Phase, Cell Cycle / drug effects
  • Retinoblastoma Protein / metabolism
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Time Factors
  • Tumor Suppressor Protein p53 / metabolism*


  • Biological Factors
  • Cyclin-Dependent Kinase Inhibitor p21
  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53
  • Cyclin D1
  • Caspase 3