HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

The high affinity peroxisome proliferator-activated receptor-gamma agonist RS5444 inhibits both initiation and progression of colon tumors in azoxymethane-treated mice.

Abstract
We evaluated RS5444, a thiazolidinedione high affinity PPARgamma agonist, for the ability to inhibit colon carcinogenesis in azoxymethane (AOM)-treated mice. In our initial experiment, mice were treated with RS5444 during AOM treatment, and the drug was withdrawn 12 weeks after the last injection of AOM. RS5444 significantly inhibited aberrant crypt focus formation under these circumstances. Furthermore, exposure to RS5444 during the course of AOM treatment effectively blocked colon tumor formation after withdrawal of the agonist. PPARgamma expression and nuclear localization were reduced in adenomas. RS5444 did not inhibit DNA synthesis in tumor cells, suggesting that PPARgamma activity was impaired in adenomas. To test this hypothesis, pre-existing adenomas were treated with RS5444 for 16 weeks. We observed a slight, albeit not statistically significant, reduction in tumor incidence in RS5444-treated mice. However, histological examination revealed that tumors from RS5444-treated mice were of significantly lower grade, as evaluated by the extent of dysplasia. Furthermore, carcinoma in situ was observed in about one-third of control tumors, but was never observed in RS5444-treated tumors. We conclude that RS5444 inhibits both initiation and progression of colon tumors in the AOM model of sporadic colon carcinogenesis.
AuthorsWeidong Su, Brian M Necela, Kosaku Fujiwara, Shinichi Kurakata, Nicole R Murray, Alan P Fields, E Aubrey Thompson
JournalInternational journal of cancer (Int J Cancer) Vol. 123 Issue 5 Pg. 991-7 (Sep 01 2008) ISSN: 1097-0215 [Electronic] United States
PMID18546290 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Anticarcinogenic Agents
  • Carcinogens
  • PPAR gamma
  • Thiazolidinediones
  • efatutazone
  • Azoxymethane
Topics
  • Animals
  • Anticarcinogenic Agents (pharmacology)
  • Azoxymethane
  • Carcinogens
  • Cell Transformation, Neoplastic (drug effects)
  • Colonic Neoplasms (chemically induced, drug therapy, pathology)
  • Disease Progression
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • PPAR gamma (agonists, analysis)
  • Thiazolidinediones (pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: