このエントリーをはてなブックマークに追加
ID 30010
フルテキストURL
著者
Tsujita-Kyutoku, Miki Department of Pathology II, Kansai Medical University
Yuri, Takashi Department of Pathology II, Kansai Medical University
Danbara, Naoyuki Department of Pathology II, Kansai Medical University
Senzaki, Hideto Department of Pathology II, Kansai Medical University
Kiyozuka, Yasuhiko Department of Pathology II, Kansai Medical University
Uehara, Norihisa Department of Pathology II, Kansai Medical University
Takada, Hideho Division of Surgery, Kansai Medical University Kori Hospital
Hada, Takahiko R&D Division, Bizen Chemical Co., Ltd
Miyazawa, Teruo Laboratory of Biodynamic Chemistry, Tohoku University Graduate School of Life Science and Agriculture
Ogawa, Yutaka Department of Plastic and Reconstructive Surgery, Kansai Medical University
Tsubura, Airo Department of Pathology II, Kansai Medical University
抄録

Introduction The present study was conducted to examine the effect of conjugated docosahexaenoic acid (CDHA) on cell growth, cell cycle progression, mode of cell death, and expression of cell cycle regulatory and/or apoptosis-related proteins in KPL-1 human breast cancer cell line. This effect of CDHA was compared with that of docosahexaenoic acid (DHA).
Methods KPL-1 cell growth was assessed by colorimetric 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; cell cycle progression and mode of cell death were examined by flow cytometry; and levels of expression of p53, p21Cip1/Waf1, cyclin D1, Bax, and Bcl-2 proteins were examined by Western blotting analysis. In vivo tumor growth was examined by injecting KPL-1 cells subcutaneously into the area of the right thoracic mammary fat pad of female athymic mice fed a CDHA diet.
Results CDHA inhibited KPL-1 cells more effectively than did DHA (50% inhibitory concentration for 72 hours: 97 μmol/l and 270 μmol/l, respectively). With both CDHA and DHA growth inhibition was due to apoptosis, as indicated by the appearance of a sub-G1 fraction. The apoptosis cascade involved downregulation of Bcl-2 protein; Bax expression was unchanged. Cell cycle progression was due to G0/G1 arrest, which involved increased expression of p53 and p21Cip1/Waf1, and decreased expression of cyclin D1. CDHA modulated cell cycle regulatory proteins and apoptosis-related proteins in a manner similar to that of parent DHA. In the athymic mouse system 1.0% dietary CDHA, but not 0.2%, significantly suppressed growth of KPL-1 tumor cells; CDHA tended to decrease regional lymph node metastasis in a dose dependent manner.
Conclusion CDHA inhibited growth of KPL-1 human breast cancer cells in vitro more effectively than did DHA. The mechanisms of action involved modulation of apoptosis cascade and cell cycle progression. Dietary CDHA at 1.0% suppressed KPL-1 cell growth in the athymic mouse system.

キーワード
apoptosis
breast cancer
conjugated docosahexaenoic acid
docosahexaenoic acid
human
備考
Digital Object Identifier:10.1186/bcr789
Published with permission from the copyright holder. This is the institute's copy, as published in Breast Cancer Research 2004, 6:R291-R299.
Publisher URL:http://dx.doi.org/10.1186/bcr789
Copyright © 2004 Tsujita-Kyutoku et al.; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL
発行日
2004-04-26
出版物タイトル
Breast Cancer Research
6巻
4号
出版者
BioMed Central
開始ページ
R291
終了ページ
R299
ISSN
1465-5411
NCID
AA11693301
資料タイプ
学術雑誌論文
言語
English
OAI-PMH Set
岡山大学
著作権者
Tsujita-Kyutoku et al.; licensee BioMed Central Ltd.
論文のバージョン
publisher
査読
有り
DOI
PubMed ID
Submission Path
surgery/3