Conjugated docosahexaenoic acid suppresses KPL-1 human breast cancer cell growth in vitro and in vivo: potential mechanisms of action.

Miki Tsujita-Kyutoku, Takashi Yuri, Naoyuki Danbara, Hideto Senzaki, Yasuhiko Kiyozuka, Norihisa Uehara, Hideho Takada, Takahiko Hada, Teruo Miyazawa, Yutaka Ogawa, Airo Tsubura

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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 micromol/l and 270 micromol/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.

Original languageEnglish
Pages (from-to)R291-299
JournalBreast cancer research : BCR
Volume6
Issue number4
DOIs
Publication statusPublished - 2004
Externally publishedYes

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Docosahexaenoic Acids
Action Potentials
Breast Neoplasms
Growth
Cell Cycle
Apoptosis
Nude Mice
Cyclin D1
In Vitro Techniques
Proteins
Cell Death
Cell Cycle Proteins
Inhibitory Concentration 50

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Conjugated docosahexaenoic acid suppresses KPL-1 human breast cancer cell growth in vitro and in vivo : potential mechanisms of action. / Tsujita-Kyutoku, Miki; Yuri, Takashi; Danbara, Naoyuki; Senzaki, Hideto; Kiyozuka, Yasuhiko; Uehara, Norihisa; Takada, Hideho; Hada, Takahiko; Miyazawa, Teruo; Ogawa, Yutaka; Tsubura, Airo.

In: Breast cancer research : BCR, Vol. 6, No. 4, 2004, p. R291-299.

Research output: Contribution to journalArticle

Tsujita-Kyutoku, M, Yuri, T, Danbara, N, Senzaki, H, Kiyozuka, Y, Uehara, N, Takada, H, Hada, T, Miyazawa, T, Ogawa, Y & Tsubura, A 2004, 'Conjugated docosahexaenoic acid suppresses KPL-1 human breast cancer cell growth in vitro and in vivo: potential mechanisms of action.', Breast cancer research : BCR, vol. 6, no. 4, pp. R291-299. https://doi.org/10.1186/bcr789
Tsujita-Kyutoku, Miki ; Yuri, Takashi ; Danbara, Naoyuki ; Senzaki, Hideto ; Kiyozuka, Yasuhiko ; Uehara, Norihisa ; Takada, Hideho ; Hada, Takahiko ; Miyazawa, Teruo ; Ogawa, Yutaka ; Tsubura, Airo. / Conjugated docosahexaenoic acid suppresses KPL-1 human breast cancer cell growth in vitro and in vivo : potential mechanisms of action. In: Breast cancer research : BCR. 2004 ; Vol. 6, No. 4. pp. R291-299.
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title = "Conjugated docosahexaenoic acid suppresses KPL-1 human breast cancer cell growth in vitro and in vivo: potential mechanisms of action.",
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 micromol/l and 270 micromol/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.",
author = "Miki Tsujita-Kyutoku and Takashi Yuri and Naoyuki Danbara and Hideto Senzaki and Yasuhiko Kiyozuka and Norihisa Uehara and Hideho Takada and Takahiko Hada and Teruo Miyazawa and Yutaka Ogawa and Airo Tsubura",
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T1 - Conjugated docosahexaenoic acid suppresses KPL-1 human breast cancer cell growth in vitro and in vivo

T2 - potential mechanisms of action.

AU - Tsujita-Kyutoku, Miki

AU - Yuri, Takashi

AU - Danbara, Naoyuki

AU - Senzaki, Hideto

AU - Kiyozuka, Yasuhiko

AU - Uehara, Norihisa

AU - Takada, Hideho

AU - Hada, Takahiko

AU - Miyazawa, Teruo

AU - Ogawa, Yutaka

AU - Tsubura, Airo

PY - 2004

Y1 - 2004

N2 - 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 micromol/l and 270 micromol/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.

AB - 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 micromol/l and 270 micromol/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.

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