Anti-tumour activity of CS-7017, a selective peroxisome proliferator-activated receptor gamma agonist of thiazolidinedione class, in human tumour xenografts and a syngeneic tumour implant model.
The anti-tumour activity of the novel thiazolidinedione class peroxisome proliferator-activated receptor gamma (PPARgamma) agonist CS-7017 was investigated. CS-7017 activated PPARgamma-mediated luciferase expression with an EC(50) of 0.20 nM. In addition, CS-7017 was shown to be highly selective for PPARgamma amongst other PPAR subfamilies. CS-7017 inhibited the proliferation of the human anaplastic thyroid tumour cell line DRO and the pancreatic tumour cell line AsPC-1 in vitro at concentrations as low as 10 nM. In xenograft studies, CS-7017 inhibited the growth of the human colorectal tumour cell line HT-29 in nude mice as well as DRO in nude rats in a dose-dependent manner. At the same dose, an increase in the levels of adiponectin, a surrogate marker for PPARgamma activation, was also observed. CS-7017 prolonged the survival of mice inoculated with murine colorectal tumour Colon 38 with marginal tumour growth inhibition. These preclinical results support the potential utility of CS-7017 in a clinical setting.
Shimazaki
Naomi
N
Biological Research Laboratories IV, Daiichi Sankyo Co, Ltd, Tokyo, Japan.
Togashi
Noriko
N
Hanai
Masaharu
M
Isoyama
Takeshi
T
Wada
Kunio
K
Fujita
Takashi
T
Fujiwara
Kosaku
K
Kurakata
Shinichi
S
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D047495:PPAR gamma / Q000819:agonists*; D045162:Thiazolidinediones / Q000378:metabolism / Q000627:therapeutic use*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D008156:Luciferases; C510342:efatutazone