This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Murata, K. Articles by Moriyama, M. Search for Related Content PubMed PubMed Citation Articles by Murata, K. Articles by Moriyama, M.

Isoleucine, an Essential Amino Acid, Prevents Liver Metastases of Colon Cancer by Antiangiogenesis

¹ The First Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie, Japan and ² Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan

Requests for reprints: Kazumoto Murata, The First Department of Internal Medicine, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie, Japan 514-8507. Phone: 81-59-231-5015; Fax: 81-59-231-5201; E-mail: atarum{at}clin.medic.mie-u.ac.jp.

In spite of recent advances in the treatment of colon cancer, multiple liver metastases of colon cancer are still difficult to treat. Some chemotherapeutic regimens have been reported to be efficient, but there is a high risk of side effects associated with these. Here, we show that isoleucine, an essential amino acid, prevents liver metastases in a mouse colon cancer metastatic model. Because isoleucine is a strong inducer of ß-defensin, we first hypothesized that it prevented liver metastases via the accumulation of dendritic cells or memory T cells through up-regulation of ß-defensin. However, neither ß-defensin nor immunologic responses were induced by isoleucine in both mouse livers and spleens. Furthermore, isoleucine prevented liver metastasis in nude mice, which lack T cells and natural killer T cells. Finally, we discovered a novel mechanism of isoleucine: down-regulation of angiogenesis via inhibition of vascular endothelial growth factor, partially through the mammalian target of the rapamycin pathway, independent of hypoxia-inducible factor 1-. Importantly, isoleucine is safe for administration to humans because it does not affect cell viability. Isoleucine could be a novel prophylactic drug for the prevention of liver metastases of colon cancer. [Cancer Res 2007;67(7):3263–8]