Pharmaceutical Research

, 25:2151

Chemoprevention of Colon Carcinogenesis by Oleanolic Acid and Its Analog in Male F344 Rats and Modulation of COX-2 and Apoptosis in Human Colon HT-29 Cancer Cells

Authors

  • Naveena B. Janakiram
    • Department of Medicine, Hem–Onc Section, OU Cancer InstituteUniversity of Oklahoma Health Sciences Center
  • Cooma Indranie
    • Department of Medicine, Hem–Onc Section, OU Cancer InstituteUniversity of Oklahoma Health Sciences Center
  • Swamy V. Malisetty
    • Department of Medicine, Hem–Onc Section, OU Cancer InstituteUniversity of Oklahoma Health Sciences Center
  • Patlolla Jagan
    • Department of Medicine, Hem–Onc Section, OU Cancer InstituteUniversity of Oklahoma Health Sciences Center
  • Vernon E. Steele
    • Chemopreventive Agent Development Research Group, Division of Cancer PreventionNCI, NIH
    • Department of Medicine, Hem–Onc Section, OU Cancer InstituteUniversity of Oklahoma Health Sciences Center
    • OU Cancer Institute, OUHSC
Research Paper

DOI: 10.1007/s11095-008-9582-7

Cite this article as:
Janakiram, N.B., Indranie, C., Malisetty, S.V. et al. Pharm Res (2008) 25: 2151. doi:10.1007/s11095-008-9582-7

Abstract

Purpose

To assess the chemopreventive effect of oleanolic acid (ONA) and its synthetic analog 18α-olean-12-ene-3β-23,28-triol (OT) on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in F344 rats and understand anti-inflammatory properties and apoptosis effects in HT29 colon cancer cells and Raw 264.7 macrophage cell lines.

Methods

Five week-old male F344 rats were fed a control diet or experimental diets containing two doses of ONA (750 and 1,500 ppm) and OT (250 and 500 ppm). After 1 week, all animals were s.c. injected with AOM (15 mg/kg body weight, once weekly for 2 weeks). At 14 weeks of age, all rats were killed and colons were evaluated for ACF. Cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) expressions and apoptosis were assessed in cell lines exposed to OT using western blots and 4’,6-diamidino-2-phenylindole staining.

Results

Administration of ONA and OT inhibited mean colonic ACF and multi-crypt AC/foci in a dose dependent manner (p < 0.001–0.0001). OT blocked the COX-2 expression induced by phorbol 12-myristate 13-acetate in a dose-dependent manner and induced apoptosis in HT-29 cancer cells, and suppressed iNOS activation in RAW264.7 macrophages.

Conclusions

ONA and OT possess chemopreventive activity against colon carcinogenesis in rat and OT inhibits the COX-2 and iNOS and induces apoptosis in cell lines.

Key words

chemopreventioncolon cancerCOX-2iNOStriterpenoids

Copyright information

© Springer Science+Business Media, LLC 2008