Chemopreventive anti-cancer agent acyclic retinoid suppresses allogeneic immune responses in rats.
Acyclic retinoid NIK-333 (ACR) is a chemopreventive agent that acts by suppressing the recurrence of hepatocellular carcinoma (HCC) following initial treatment and is now being employed in clinical trials. The chemopreventive effects of ACR have been analyzed from various aspects, and it is well known that some retinoic acid (RA) derivatives affect host immunity. The objective of this study is to investigate the effects of ACR on host immunity. The results demonstrated that ACR prolonged heart and liver graft and recipient survival in rat allogeneic organ transplantation. The immunosuppressive effect of ACR administered at 100mg/kg/day was almost equivalent to that of CsA administered at 1mg/kg/day in vivo. In the mixed lymphocyte reaction (MLR), ACR suppressed lymphocyte proliferation non-specifically. Gene expression analysis of splenic lymphocytes from ACR-treated recipient rats revealed no distinct change in Interleukin (IL)-2 and increases in Interferon (IFN)-gamma. In conclusion, ACR possesses immunosuppressive potential in vivo and is a promising chemopreventive drug for long term use against HCC.
Ohsawa
Ichiro
I
Division of Organ Replacement Research, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan. ohsawa-i@clin.medic.mie-u.ac.jp
Murakami
Takashi
T
Guo
Lei
L
Enosawa
Shin
S
Ishibashi
Naoto
N
Isaji
Shuji
S
Uemoto
Shinji
S
Kobayashi
Eiji
E
D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology; D016027:Heart Transplantation; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D016031:Liver Transplantation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D012176:Retinoids / Q000008:administration & dosage*; D014184:Transplantation, Homologous; D014212:Tretinoin / Q000008:administration & dosage* / Q000031:analogs & derivatives
D016588:Anticarcinogenic Agents; D012176:Retinoids; C487689:(2E,4E,6E,10E)-3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid; D014212:Tretinoin; D007371:Interferon-gamma; D016572:Cyclosporine