Cancer chemopreventive effects of cycloartane-type and related triterpenoids in in vitro and in vivo models

J Nat Prod. 2007 Jun;70(6):918-22. doi: 10.1021/np068044u. Epub 2007 May 16.

Abstract

Forty-eight natural and semisynthetic cycloartane-type and related triterpenoids have been evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells as a primary screening test for anti-tumor promoters. In addition, these triterpenoids have been tested for their inhibitory effects on activation of (+/-)-(E)-methtyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitric oxide (NO) donor, as a primary screening test for anti-tumor initiators. All of the compounds tested exhibited inhibitory effects on both EBV-EA and NOR 1 activation. Six of these compounds having a C-24 hydroxylated side chain, viz., (24R)-cycloart-25-ene-3beta,24-diol (9), (24R)-cycloartane-3beta,24,25-triol (11), (24S)-cycloartane-3beta,24,25-triol (12), (24xi)-24-methylcycloartane-3beta,24,241-triol (14), (24xi)-241-methoxy-24-methylcycloartane-3beta,24-diol (15), and (24xi)-24,25-dihydroxycycloartan-3-one (27), showed higher inhibitory effects than the others tested on both EBV-EA (IC50 values of 6.1-7.4 nM) and NOR 1 activation. Furthermore, compounds 14 and 15 exhibited inhibitory effects on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Anticarcinogenic Agents / chemistry*
  • Anticarcinogenic Agents / pharmacology*
  • Antigens, Viral / drug effects*
  • Dose-Response Relationship, Drug
  • Mice
  • Models, Biological*
  • Molecular Structure
  • Skin / drug effects
  • Tetradecanoylphorbol Acetate / pharmacology
  • Time Factors
  • Triterpenes / chemistry*
  • Triterpenes / pharmacology*

Substances

  • Anticarcinogenic Agents
  • Antigens, Viral
  • Epstein-Barr virus early antigen
  • Triterpenes
  • cycloartane
  • Tetradecanoylphorbol Acetate