Delayed occurrence of H-ras12V-induced hepatocellular carcinoma with long-term treatment with cinnamaldehydes.
Cinnamaldehyde from the bark of Cinnamomum cassia has been reported to have antitumor activity mediated by the inhibition of farnesyl transferase. We assessed in vivo the chemo-preventive effect of cinnamaldehydes on H-ras12V-induced hepatocellular carcinoma formation. A mouse model of hepatocellular carcinoma was established by using the transgene of mutated H-ras12V under the regulation of albumin enhancer/promoter. When treated with cinnamaldehyde for 10 weeks, hepatic tumor development was delayed with 2'-benzoyloxycinnamaldehyde (BCA) compared with control hepatocellular carcinoma formation. The effect of 2'-hydroxycinnamaldehyde (HCA) was comparable. The number of lesions and the size of each lesion were significantly reduced by BCA. Cell proliferation in the lesion was detected by incorporation of 5-bromo-2'-deoxyuridine (BrdU). BCA increased the number of splenocytes, concanavalin A-stimulated splenocyte proliferation and the infiltration of lymphocytes into liver. Data suggest that the delayed hepatic tumor development observed with BCA could be mediated by a long-term immunostimulating effect on T cells.
Moon
Eun-Yi
EY
Department of Human Genomics, Korea Research Institute of Bioscience and Biotechnology, 52 Oun-Dong, Yusong-Gu, Taejeon 305-806, Korea. eunyi@kribb.re.kr
Lee
Mi-Ran
MR
Wang
Ai-Guo
AG
Lee
Jun-Hee
JH
Kim
Hyoung-Chin
HC
Kim
Hwan-Mook
HM
Kim
Jin-Man
JM
Kwon
Byoung-Mog
BM
Yu
Dae-Yeul
DY
D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D011905:Genes, ras / Q000235:genetics; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D013154:Spleen / Q000166:cytology; D047368:Tumor Burden / Q000187:drug effects
C484327:2'-benzoyloxycinnamaldehyde; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D001565:Benzoates; D000171:Acrolein; C012843:cinnamaldehyde