title: [Gamma-hydroxybutyric acid, a metabolite of UFT, shows anti-angiogenic activities and antitumor effect].
abstract: We investigated the antitumor vasculogenesis and antitumor activity of gamma-hydroxybutyric acid (GHB), a metabolite of UFT. In a mouse dorsal air sac (DAS) assay, UFT demonstrated a wide spectrum of anti-tumor vasculogenesis except for AZ-521 tumor. Although the expression of vascular endothelial growth factor (VEGF) was detected in almost all tumor cell lines used in the DAS assays, expression of basic fibroblast growth factor (bFGF) was only detected in the AZ-521 tumor. GHB inhibited the chemotactic migration and morphological changes of human umbilical vein endothelial cells (HUVECs) induced by VEGF at IC50 values of 2.8 and 0.31 microM respectively. In addition to these in vitro assays, GHB blocked tumor growth of MC-5, a human breast cancer, in a xenograft model at inhibition rate of 37%. Moreover, GHB showed an additive effect in combination with 5-FU in this model. These results indicate that the anti-tumor vasculogenesis activity of GHB is involved in part in the antitumor effect of UFT.
authors.affiliation: Cancer Research Laboratory, Taiho Pharmaceutical Co., Ltd.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Basaki
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Miyadera
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yonekura
authors.forename: Kumio
authors.initials: K
authors.lastname: Aoyagi
authors.forename: Lumi
authors.initials: L
authors.lastname: Chikahisa
authors.forename: Soko
authors.initials: S
authors.lastname: Okabe
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hashimoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Kitazato
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004338:Drug Combinations; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D005770:Gastrointestinal Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007680:Kidney Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008222:Lymphokines / Q000096:biosynthesis; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012978:Sodium Oxybate / Q000494:pharmacology*; D005641:Tegafur / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014498:Uracil / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D004338:Drug Combinations; D016228:Endothelial Growth Factors; D008222:Lymphokines; C096910:UFT(R) drug; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D005641:Tegafur; D014498:Uracil; D012978:Sodium Oxybate