Cancer preventive agents. Part 1: chemopreventive potential of cimigenol, cimigenol-3,15-dione, and related compounds

Bioorg Med Chem. 2005 Feb 15;13(4):1403-8. doi: 10.1016/j.bmc.2004.10.062.

Abstract

In continuation of our previous report, cimigenol (1) and 15 related compounds were screened as potential antitumor promoters by using the in vitro short-term 12-O-tetradecanoylphorbol-13-acetate (TPA)--induced Epstein-Barr virus early antigen (EBV-EA) activation assay. Cimigenol-3,15-dione (2) displayed the greatest potency (100% inhibition at 1000 mol ratio/TPA) and consequently was further examined for antitumor-promoting activity in a two-stage carcinogenesis assay of mouse skin tumors (DMBA/TPA). In this assay, compound 2 showed significant activity, reducing the number of papillomas per mouse to 48% of the control group at 20 weeks. In addition, compounds 1 and 2 were examined for antitumor-initiating activity in a two-stage carcinogenesis assay of mouse skin tumors induced by peroxynitrite as an initiator and TPA as a promoter. Results showed that these two triterpenoids were almost equipotent with epigallocatechin gallate (EGCG) and slightly more potent than tocinol (group V), the positive controls. Thus, compounds 1 and 2 exhibited not only strong antitumor-promoting activity but also significant antitumor-initiating effect on mouse skin. These data suggest that both compounds might be valuable chemopreventors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anticarcinogenic Agents / chemistry
  • Anticarcinogenic Agents / pharmacology*
  • Female
  • Lanosterol / analogs & derivatives*
  • Lanosterol / chemistry
  • Lanosterol / pharmacology*
  • Mice
  • Mice, Inbred ICR
  • Papilloma / prevention & control
  • Skin Neoplasms / prevention & control

Substances

  • (23R,24S)-16,23-16,24-diepoxy-9,19-cyclolanostan-3beta,15alpha,25-triol
  • Anticarcinogenic Agents
  • Lanosterol