Cancer preventive agents. Part 1: chemopreventive potential of cimigenol, cimigenol-3,15-dione, and related compounds.
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.
Sakurai
Nobuko
N
Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7360, USA.
Kozuka
Mutsuo
M
Tokuda
Harukuni
H
Mukainaka
Teruo
T
Enjo
Fumio
F
Nishino
Hoyoku
H
Nagai
Masahiro
M
Sakurai
Yojiro
Y
Lee
Kuo-Hsiung
KH
D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D010212:Papilloma / Q000517:prevention & control; D012878:Skin Neoplasms / Q000517:prevention & control
C478830:(23R,24S)-16,23-16,24-diepoxy-9,19-cyclolanostan-3beta,15alpha,25-triol; D016588:Anticarcinogenic Agents; D007810:Lanosterol