TY - JOUR
T1 - Inhibitory effects of isoflavones on tumor growth and cachexia in newly established cachectic mouse models carrying human stomach cancers
AU - Yanagihara, Kazuyoshi
AU - Takigahira, Misato
AU - Mihara, Keichiro
AU - Kubo, Takanori
AU - Morimoto, Chie
AU - Morita, Yasuhiro
AU - Terawaki, Kiyoshi
AU - Uezono, Yasuhito
AU - Seyama, Toshio
N1 - Funding Information:
This work was supported by a Grant-in-Aid for the Third-Term Comprehensive 10-year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare, Japan; a Grant-in-Aid for Scientific Research (C) from Ministry of Education, Culture, Sports, Science and Technology, Japan; the National Cancer Center Research and Development Fund (23-A-2); and the Foundation for Promotion of Cancer Research in Japan. We are grateful to Professor Emeritus Dr. A. Ito (Hiroshima University, Hiroshima, Japan) and Dr. M. Takebe (Nichimo Co., Ltd., Tokyo, Japan) for helpful discussions and providing the generous gift. We thank Professor Emeritus Dr. T. Suzuki (Fukushima Medical University, Fukushima, Japan) for the supply of 3 stomach cancer cell lines. We also thank R. Nakanishi, T. Komatsu, and K. Otsubo for their excellent technical assistance.
PY - 2013/5/1
Y1 - 2013/5/1
N2 - Cachexia, a negative prognostic factor, worsens a patient's quality of life. We established 2 novel cachexia models with the human stomach cancer cell line MKN-45, which was subcloned to produce potent cachexia-inducing cells by repeating the xenografts in immune-deficient mice. After subsequent xenografts, we isolated potent cachexia-inducing cells (MKN45cl85 and 85As2mLuc). Xenografts of MKN45cl85 cells in mice led to substantial weight loss and reduced adipose tissue and musculature volumes, whereas xenografts of 85As2mLuc cells resulted in highly metastatic and cachectic mice. Surgical removal of tumor tissues helped the mice regain body-weight in both mouse models. In vitro studies using these cells showed that isoflavones reduced their proliferation, implying that the isoflavones possess antiproliferative effects of these cancer cell lines. Isoflavone treatment on the models induced tumor cytostasis, attenuation of cachexia, and prolonged survival whereas discontinuation of the treatment resulted in progressive tumor growth and weight loss. The inhibitory effects of tumor growth and weight loss by isoflavones were graded as soy isoflavone aglycone AglyMax > daidzein > genistein. These results demonstrated that the 2 novel cachectic mouse models appear useful for analyzing the mechanism of cancer cachexia and monitoring the efficacy of anticachectic agents.
AB - Cachexia, a negative prognostic factor, worsens a patient's quality of life. We established 2 novel cachexia models with the human stomach cancer cell line MKN-45, which was subcloned to produce potent cachexia-inducing cells by repeating the xenografts in immune-deficient mice. After subsequent xenografts, we isolated potent cachexia-inducing cells (MKN45cl85 and 85As2mLuc). Xenografts of MKN45cl85 cells in mice led to substantial weight loss and reduced adipose tissue and musculature volumes, whereas xenografts of 85As2mLuc cells resulted in highly metastatic and cachectic mice. Surgical removal of tumor tissues helped the mice regain body-weight in both mouse models. In vitro studies using these cells showed that isoflavones reduced their proliferation, implying that the isoflavones possess antiproliferative effects of these cancer cell lines. Isoflavone treatment on the models induced tumor cytostasis, attenuation of cachexia, and prolonged survival whereas discontinuation of the treatment resulted in progressive tumor growth and weight loss. The inhibitory effects of tumor growth and weight loss by isoflavones were graded as soy isoflavone aglycone AglyMax > daidzein > genistein. These results demonstrated that the 2 novel cachectic mouse models appear useful for analyzing the mechanism of cancer cachexia and monitoring the efficacy of anticachectic agents.
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U2 - 10.1080/01635581.2013.776089
DO - 10.1080/01635581.2013.776089
M3 - Article
C2 - 23659450
AN - SCOPUS:84877944664
SN - 0163-5581
VL - 65
SP - 578
EP - 589
JO - Nutrition and Cancer
JF - Nutrition and Cancer
IS - 4
ER -