Prevention of rat hepatocarcinogenesis by acyclic retinoid is accompanied by reduction in emergence of both TGF-alpha-expressing oval-like cells and activated hepatic stellate cells.

Abstract

We investigated the preventive effects of a synthetic acyclic retinoid, NIK-333, on the early and late events of hepatocarcinogenesis in male F344 rats treated with 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB). NIK-333 was administered once a day on consecutive days at a dose of 10, 40, or 80 mg/kg body weight along with the supplementation with 3'-MeDAB-containing diet for 16 wk. Animals from each group were sacrificed at 4 and 16 wk after the commencement of the experiment to determine the effect of NIK-333 on the early and late stages of carcinogenesis, respectively. NIK-333 suppressed the emergence of both oval-like cells expressing transforming growth factor (TGF)-alpha, putative progenitors of hepatocellular carcinoma (HCC), and activated hepatic stellate cells, major matrix-producing cells of the liver, in the early stage and inhibited the incidence of HCC in the late phase. These results suggest that NIK-333 is a promising drug for the chemoprevention of HCC by uniquely suppressing the early events of hepatocarcinogenesis, that is, development of both oval-like cells and fibrogenesis.

• Authors: Tetsuro Sano, Masataka Kagawa, Masataka Okuno, Naoto Ishibashi, Manabu Hashimoto, Megumi Yamamoto, Rikako Suzuki, Hiroyuki Kohno, Rie Matsushima-Nishiwaki, Yukihiko Takano, Hisashi Tsurumi, Soichi Kojima, Scott L Friedman, Hisataka Moriwaki, Takuji Tanaka
• Journal: Nutrition and cancer (Nutr Cancer) Vol. 51 Issue 2 Pg. 197-206 ( 2005) ISSN: 0163-5581 [Print] United States
• PMID: 15860442 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Actins
• Antineoplastic Agents
• Retinoids
• Transforming Growth Factor alpha
• smooth muscle actin, rat
• (2E,4E,6E,10E)-3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid
• 3'-methyl-4-diethylaminoazobenzene
• Methyldimethylaminoazobenzene
• Tretinoin
• 3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid

Topics

• Actins (drug effects, metabolism)
• Adenoma (chemically induced, prevention & control)
• Animals
• Antineoplastic Agents (chemistry, therapeutic use)
• Carcinoma (chemically induced, prevention & control)
• Disease Models, Animal
• Disease Progression
• Dose-Response Relationship, Drug
• Fibrosis (prevention & control)
• Liver (drug effects, metabolism)
• Liver Neoplasms, Experimental (chemically induced, prevention & control)
• Male
• Methyldimethylaminoazobenzene (administration & dosage, analogs & derivatives)
• Rats
• Rats, Inbred F344
• Retinoids (therapeutic use)
• Reverse Transcriptase Polymerase Chain Reaction (methods)
• Time Factors
• Transforming Growth Factor alpha (drug effects, metabolism)
• Tretinoin (analogs & derivatives, chemistry, therapeutic use)