Visit our Expo - Redox and Inflammation signaling 2012

Session X : Cell death in cancer Poster X, 46
Cytoplasmic fraction of Lactococcus latic ssp. Lactis induces apoptosis and G0/G1 cell
cycle arrest in SNU1 human stomach cancer cells
Seo Young Kim, Ki Won Lee, Min A Jeong, Ji Yeon Kim, and Hyong Joo Lee*
Department of Food Biotechnology, School of Agricultural Biotechnology, and Center
for
Agricultural Biomaterials, Seoul National University, Seoul 151-742, Republic of Korea
Lactic acid bacteria are known to have antitumor activity, but the underlying mechanisms
remain unclear. The present study investigated antiproliferative activity of cytoplasmic
fraction of Lactococcus latic ssp. (L.lac CF) on SNU-1 human stomach cancer cell line (SNU-
1 cells) and underlying molecular mechanisms. The proliferation of SNU-1 cells was
inhibited by the treatment of L.lac CF in a time- and dose-dependent. In addition, L.lac CF
showed a significantly more relevant G0/G1 cell cycle arrest, which associated increase of
p21 and reduction of cyclin D1 and phosphorylation level of Rb. Furthermore, L.lac CF
induced apoptosis of SNU-1 cells, but not SNU-C2A human colon cancer cells, as evidenced
by nuclei condensation, increase of sub-G1 peak, and DNA fragmentation. In particular, p53
and bcl-2 appears to play a critical role in the apoptosis of SNU-1 cells by L.lac CF. We
further investigated if arginine deiminase (ADI) is involved in the antiproliferative activity of
L.lac CF, since arginine is known as essential amino acid for growing cells. Surprisingly, only
L.lac CF, which showed significantly strong antiproliferative activity and ADI activity among
tested six LAB. The concentration of L.lac CF showed linear relationship with both ADI
activity and antiproliferative activity. Furthermore, addition of L-arginine recover the
antiproliferative activity of L.lac CF. We purified ADI from L.lac CF by subsequent
fractionations, and the IC50 value of final ADI fraction was 2 µg/ml. The ADI fraction also
exerted apoptosis as evidenced by nuclei condensation in cells. These results, taken together,
indicate that the antiproliferative activity of L.lac CF on SNU-1 is attributable to induction of
G0/G1 cell cycle arrest and apoptosis, particularly the latter one by ADI.
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