start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=4 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2004 dt-pub=20040615 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Addition of granulocyte-colony stimulating factor (G-CSF) may further increase chemosensitive state in premenopausal node-positive breast cancer patients with induced angiogenesis after surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=AltundagKadri en-aut-sei=Altundag en-aut-mei=Kadri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AltundagOzden en-aut-sei=Altundag en-aut-mei=Ozden kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GunduzMehmet en-aut-sei=Gunduz en-aut-mei=Mehmet kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=Department of Medical Oncology, Hacettepe University Faculty of Medicine affil-num=2 en-affil= kn-affil=Department of Medical Oncology, Hacettepe University Faculty of Medicine affil-num=3 en-affil= kn-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine and Dentistry, Okayama University END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=4 article-no= start-page=R291 end-page=R299 dt-received= dt-revised= dt-accepted= dt-pub-year=2004 dt-pub=20040426 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Conjugated docosahexaenoic acid suppresses KPL-1 human breast cancer cell growth in vitro and in vivo: potential mechanisms of action en-subtitle= kn-subtitle= en-abstract= kn-abstract=

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 ƒÊmol/l and 270 ƒÊmol/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.

en-copyright= kn-copyright= en-aut-name=Tsujita-KyutokuMiki en-aut-sei=Tsujita-Kyutoku en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YuriTakashi en-aut-sei=Yuri en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DanbaraNaoyuki en-aut-sei=Danbara en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SenzakiHideto en-aut-sei=Senzaki en-aut-mei=Hideto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KiyozukaYasuhiko en-aut-sei=Kiyozuka en-aut-mei=Yasuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UeharaNorihisa en-aut-sei=Uehara en-aut-mei=Norihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakadaHideho en-aut-sei=Takada en-aut-mei=Hideho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HadaTakahiko en-aut-sei=Hada en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiyazawaTeruo en-aut-sei=Miyazawa en-aut-mei=Teruo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OgawaYutaka en-aut-sei=Ogawa en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TsuburaAiro en-aut-sei=Tsubura en-aut-mei=Airo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil= kn-affil=Department of Pathology II, Kansai Medical University affil-num=2 en-affil= kn-affil=Department of Pathology II, Kansai Medical University affil-num=3 en-affil= kn-affil=Department of Pathology II, Kansai Medical University affil-num=4 en-affil= kn-affil=Department of Pathology II, Kansai Medical University affil-num=5 en-affil= kn-affil=Department of Pathology II, Kansai Medical University affil-num=6 en-affil= kn-affil=Department of Pathology II, Kansai Medical University affil-num=7 en-affil= kn-affil=Division of Surgery, Kansai Medical University Kori Hospital affil-num=8 en-affil= kn-affil=R&D Division, Bizen Chemical Co., Ltd affil-num=9 en-affil= kn-affil=Laboratory of Biodynamic Chemistry, Tohoku University Graduate School of Life Science and Agriculture affil-num=10 en-affil= kn-affil=Department of Plastic and Reconstructive Surgery, Kansai Medical University affil-num=11 en-affil= kn-affil=Department of Pathology II, Kansai Medical University en-keyword=apoptosis kn-keyword=apoptosis en-keyword=breast cancer kn-keyword=breast cancer en-keyword=conjugated docosahexaenoic acid kn-keyword=conjugated docosahexaenoic acid en-keyword=docosahexaenoic acid kn-keyword=docosahexaenoic acid en-keyword=human kn-keyword=human END