Delayed occurrence of H-ras12V-induced hepatocellular carcinoma with long-term treatment with cinnamaldehydes

Eur J Pharmacol. 2006 Jan 20;530(3):270-5. doi: 10.1016/j.ejphar.2005.11.053.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrolein / analogs & derivatives*
  • Acrolein / pharmacology
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Benzoates / pharmacology*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology
  • Cell Proliferation / drug effects
  • Female
  • Genes, ras / genetics
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Liver Neoplasms, Experimental / drug therapy
  • Liver Neoplasms, Experimental / genetics
  • Liver Neoplasms, Experimental / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • NIH 3T3 Cells
  • Spleen / cytology
  • Tumor Burden / drug effects

Substances

  • 2'-benzoyloxycinnamaldehyde
  • Antineoplastic Agents
  • Antineoplastic Agents, Phytogenic
  • Benzoates
  • Acrolein
  • cinnamic aldehyde