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Antiproliferative mechanisms of cytoplasmic fraction and arginine deiminase from Lactococcus lactis ssp. lactis on a human stomach cancer cell line

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Authors
김서영
Advisor
이형주
Issue Date
2004
Publisher
서울대학교 대학원
Keywords
락토코코스 락티스Lactococcus lactis ssp. lactis세포질Cytoplasmic fraction사람의 위암 세포주 SNU-1Human stomach cell lineG0/G1 세포주기저해Snu-1 cells세포자가사멸G0/g1 cell cycle arrest아르기닌 디이미네이즈ApoptosisArginine deiminase
Description
Thesis (master`s)--서울대학교 대학원 :농생명공학부,2004.
Abstract
Lactic acid bacteria are known to have antitumor activity, but the underlying mechanisms remain
unclear. Our previous study have demonstrated that cytoplasmic fraction of Lactococcus lactis
ssp. lactis (L.lac CF) inhibited the proliferation of SNUC2A human colon cancer cell line
(SNUC2A cells), through induction of S phase accumulation. The present study investigated if the
antiproliferative mechanisms of L.lac CF on SNU-1 human stomach cancer cell line (SNU-1 cells)
linked to the induction of cell cycle arrest and apoptosis, and to find potential antiproliferative
compounds in L.lac CF. 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 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. 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 Larginine
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 cells may be
contributable to induction of G0/G1 cell cycle arrest and apoptosis, particularly the latter one
by ADI.
Language
English
URI
http://dcollection.snu.ac.kr:80/jsp/common/DcLoOrgPer.jsp?sItemId=000000055057

http://hdl.handle.net/10371/67593
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College of Agriculture and Life Sciences (농업생명과학대학)Dept. of Food and Animal Biotechnology (식품·동물생명공학부)Theses (Master's Degree_식품·동물생명공학부)
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