Research Project
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.
All 2017 2016 2015 2014 2013 Other
All Journal Article (17 results) (of which Int'l Joint Research: 3 results, Peer Reviewed: 17 results, Open Access: 11 results, Acknowledgement Compliant: 10 results) Presentation (37 results) Book (1 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)
Cancer Sci
Volume: 107 Issue: 7 Pages: 924-935
10.1111/cas.12954
Advanced Drug Delivery Reviews
Volume: 99 Pages: 206-211
10.1016/j.addr.2015.11.017
Microbiology and Immunology, Epub
Volume: 60 Issue: 1 Pages: 35-46
10.1111/1348-0421.12338
Oncology Letters
Volume: 9 Issue: 5 Pages: 2112-2118
10.3892/ol.2015.3053
Chemokine (C-C motif) ligand 3 detection in the serum of persons exposed to asbestos: A patient-based study
Volume: 106 Issue: 7 Pages: 2112-2118
10.1111/cas.12687
PLoS One
Volume: 9 Issue: 10 Pages: 268-274
10.1371/journal.pone.0111481
Biol Pharm Bull
Volume: 37 Pages: 1068-1074
130004147355
Biometals
Volume: 27 Issue: 5 Pages: 1017-1029
10.1007/s10534-014-9747-2
Volume: 105 Issue: 7 Pages: 763-769
10.1111/cas.12437
Asian Pac J Cancer Prev
Volume: 15 Pages: 929-935
Archives of toxicology
Volume: 88 Issue: 1 Pages: 65-75
10.1007/s00204-013-1086-5
Journal of Toxicologic Pathology
Volume: 26 Issue: 4 Pages: 335-341
10.1293/tox.2013-0028
130003382464
Oncology reports
Volume: 30 Issue: 1 Pages: 64-70
10.3892/or.2013.2441
Genesis
Volume: 51 Issue: 4 Pages: 268-274
10.1002/dvg.22371
Carcinogenesis
Volume: 34 Issue: 6 Pages: 1251-1259
10.1093/carcin/bgt053
Pancreas
Volume: 42 Pages: 1034-1039
Molecular Oncology
Volume: 7 Issue: 1 Pages: 14-28
10.1016/j.molonc.2012.10.009
http://www.med.nagoya-cu.ac.jp/moltox.dir/index.html