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Pharmaceutical Research

, 25:2151 | Cite as

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

  • Naveena B. Janakiram
  • Cooma Indranie
  • Swamy V. Malisetty
  • Patlolla Jagan
  • Vernon E. Steele
  • Chinthalapally V. Rao
Research Paper

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

chemoprevention colon cancer COX-2 iNOS triterpenoids 

Notes

Acknowledgement

We gratefully acknowledge NCI chemoprevention drug development repository for providing oleanolic acid analog OT. We also extend our thanks to Ms. Alyson Atchison for editing this article.

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Naveena B. Janakiram
    • 1
  • Cooma Indranie
    • 1
  • Swamy V. Malisetty
    • 1
  • Patlolla Jagan
    • 1
  • Vernon E. Steele
    • 2
  • Chinthalapally V. Rao
    • 1
    • 3
  1. 1.Department of Medicine, Hem–Onc Section, OU Cancer InstituteUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA
  2. 2.Chemopreventive Agent Development Research Group, Division of Cancer PreventionNCI, NIHBethesdaUSA
  3. 3.OU Cancer Institute, OUHSCOklahoma CityUSA

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