Grant-in-Aid for Scientific Research (C)
We developed a novel anticancer drug, palmitoyl piperidinopiperidine (PPI). In silico simulation exhibited that PPI can bind SH2 domain of STAT3, indicating that this drug blocks dimerization of STAT3, thereby inactivates its function. PPI inhibited transcriptional activity of STAT3, and induced G1 arrest/apoptosis in colon carcinoma cells. There was a marked decrease in expression levels of the Bcl-2, Bcl-xL, and VEGF proteins and an increase in those of the cleaved caspase 3, 7, 8, 9 and PARP proteins. PPI inhibited nuclear translocation of pSTAT3. PPI caused a dose dependent decrease in multiplicity of carcinogen-induced ACF in the rat colon. In a xenograft model, PPI decreased the size and number of blood vessels in the tumor. CAM assays showed a dose-dependent decrease in number of blood vessels. Inhibition of STAT3 by PPI affects the function of molecules related to apoptosis, angiogenesis and cell cycle progression, and contributes to growth inhibition of tumor cells.
Patent(Industrial Property Rights)
Adv Drug Deliv Rev
Biol Pharm Bull
Asian Pac J Cancer Prev
J Toxicol Pathol
Attribution of KAKENHI