Inhibitory effects of asiatic acid on 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol 13-acetate-induced tumor promotion in mice

Biol Pharm Bull. 2007 Jan;30(1):176-9. doi: 10.1248/bpb.30.176.

Abstract

Asiatic acid, a pentacyclic triterpene, has been reported to induce apoptosis of various human cancer cells. In the present study, we assessed the anti-tumor promoting effect of asiatic acid against 12-O-tetradecanoylphorbol 13-acetate (TPA)-mediated skin tumorigenesis in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated ICR mice. Topical application of asiatic acid prior to each application of TPA resulted in a significant reduction in skin tumor formation. We also found that pre-application of asiatic acid alleviated TPA-induced [3H]thymidine incorporation, which is a conventional marker for skin tumor promotion. In addition, asiatic acid inhibited the TPA-induced generation of nitric oxide (NO) and expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), which are known to play important roles in tumor growth, especially in the promotion stage. In addition, topical application of aminoguanidine (AG), a selective iNOS inhibitor, and N(G)-nitro-L-arginine-methyl ester (NAME), another iNOS inhibitor, 30 min prior to TPA treatment significantly inhibited the TPA-induced COX-2 expression. These results suggest that asiatic acid may exert anti-tumorigenesis through inhibitory actions in NO and COX-2 signals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene
  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Anticarcinogenic Agents / therapeutic use
  • Carcinogens
  • Cell Transformation, Neoplastic / drug effects
  • Cocarcinogenesis
  • Cyclooxygenase 2 / biosynthesis
  • Dose-Response Relationship, Drug
  • Enzyme Induction / drug effects
  • Female
  • Mice
  • Mice, Inbred ICR
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / biosynthesis
  • Papilloma / chemically induced
  • Papilloma / prevention & control*
  • Pentacyclic Triterpenes
  • Skin / drug effects*
  • Skin / metabolism
  • Skin Neoplasms / chemically induced
  • Skin Neoplasms / prevention & control*
  • Tetradecanoylphorbol Acetate
  • Time Factors
  • Triterpenes / pharmacology*
  • Triterpenes / therapeutic use

Substances

  • Anticarcinogenic Agents
  • Carcinogens
  • Pentacyclic Triterpenes
  • Triterpenes
  • Nitric Oxide
  • 9,10-Dimethyl-1,2-benzanthracene
  • asiatic acid
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Cyclooxygenase 2
  • Tetradecanoylphorbol Acetate