Antimetastatic and antitumor effects of 2,4-diamino-6-(pyridine-4-yl)-1,3,5-triazine (4PyDAT) on the high lung metastatic colon 26 tumor in mice.
The therapeutic potential of a diaminotriazine, 2,4-diamino-6-(pyridine-4-yl)-1,3,5-triazine (4PyDAT), was investigated in a metastatic model using the mouse colon 26 carcinoma variant (Co26Lu), which preferentially metastasizes to the lung of mouse. The compound had a moderate antimetastatic activity as well as antitumor activity, without toxicity to the host, when administered orally. In the cytotoxicity test in vitro, 4PyDAT showed very weak direct cytotoxicity against the Co26Lu cell line, Co26Lu(F55) (IC50 < or = 1000 microM). Less microcapiral formation on tumors were observed for the treated group with a hemorrhage than the control group under microscopy. 4PyDAT significantly inhibited the production of urokinase-type plasminogen activator (u-PA) in Co26Lu(F55) cells. These results suggest that the antimetastatic and antitumor activities of 4PyDAT are due in part to inhibition of angiogenesis, rather than direct antiproliferative action on the tumor cells. 4PyDAT may become a lead compound to develop antitumor triazine derivatives based on antiangiogenic action.
Maeda
M
M
Experimental Pathology and Chemotherapy Division, National Cancer Center Research Institute, Tokyo, Japan.
Ligo
M
M
Tsuda
H
H
Fujita
H
H
Yonemura
Y
Y
Nakagawa
K
K
Endo
Y
Y
Sasaki
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D008175:Lung Neoplasms / Q000098:blood supply / Q000201:enzymology / Q000517:prevention & control* / Q000556:secondary*; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D011725:Pyridines / Q000494:pharmacology*; D014227:Triazines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors
C414984:2,4-diamino-6-(pyridine-4-yl)-1,3,5-triazine; D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D011725:Pyridines; D014227:Triazines; D014568:Urokinase-Type Plasminogen Activator