HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Enhancement of transformed foci and induction of prostaglandins in Balb/c 3T3 cells by palytoxin: in vitro model reproduces carcinogenic responses in animal models regarding the inhibitory effect of indomethacin and reversal of indomethacin's effect by exogenous prostaglandins.

Abstract
Cell transforming activity of palytoxin, a non-TPA type tumor-promoter, was investigated with the two-stage transformation assay using Balb/c 3T3 cells. Palytoxin showed potent promoting activity; treatment at 1.9 pM or more increased the number of transformed foci after initiation by 3-methylcholanthrene (MCA). Determination of prostaglandin (PG) E2 and PGF(2alpha) concentrations in the culture medium revealed that palytoxin (1.9-3.7 pM for 24 h) stimulated the production of PG in Balb/c 3T3 cells (the concentration reached 3-4 microM), and treatment with PGE2 or PGF(2alpha) itself increased the number of transformed foci of Balb/c 3T3 cells after initiation by MCA. Neither palytoxin nor PGs showed initiating activity. Indomethacin suppressed the promoting activity of palytoxin, but not that of PGE2 and PGF(2alpha). Interestingly, concomitant treatment with PGE2 or PGF(2alpha) in addition to indomethacin markedly reversed the suppressive effect of indomethacin. These findings indicated that the in vitro transformation model could reproduce experiments that have been performed in animal models regarding the inhibitory effect of indomethacin on carcinogenic responses and reversal of indomethacin's effect by exogenous prostaglandin and, therefore, may provide insight into molecular modes of action of palytoxin. In the present study, palytoxin also induced prostaglandin synthesis, and therefore, the Balb/c 3T3 cell model should provide insight into the molecular mechanism by which palytoxin regulates prostaglandin biosynthesis.
AuthorsDaishiro Miura, Mitsuru Kobayashi, Satoko Kakiuchi, Yoshinori Kasahara, Shiro Kondo
JournalToxicological sciences : an official journal of the Society of Toxicology (Toxicol Sci) Vol. 89 Issue 1 Pg. 154-63 (Jan 2006) ISSN: 1096-6080 [Print] United States
PMID16192471 (Publication Type: Journal Article)
Chemical References
  • Acrylamides
  • Carcinogens
  • Cnidarian Venoms
  • Drug Combinations
  • Methylcholanthrene
  • Dinoprost
  • Dinoprostone
  • palytoxin
  • Indomethacin
Topics
  • Acrylamides (toxicity)
  • Animals
  • BALB 3T3 Cells
  • Carcinogens (toxicity)
  • Cell Transformation, Neoplastic (drug effects)
  • Cnidarian Venoms (toxicity)
  • Dinoprost (biosynthesis, pharmacology)
  • Dinoprostone (biosynthesis, pharmacology)
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Antagonism
  • Drug Combinations
  • Indomethacin (pharmacology)
  • Methylcholanthrene (toxicity)
  • Mice

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: