Phorbol related esters have similar structure-activity relations in Swiss 3T3 cells and chicken embryo fibroblasts.

Abstract

We have examined the activity of nine phorbol-related diterpene esters for stimulation of 2-deoxyglucose uptake in the Swiss 3T3 mouse cell line. The half-maximally effective doses (ED50's) of these derivatives ranged over four orders of magnitude. The potencies of the seven phorbol esters studied correlated well with their previously determined potencies in vitro for stimulation of 2-deoxyglucose uptake in chicken embryo fibroblasts and with thier potencies in vivo in the mouse ear inflammation assay. Two esters of 12-deoxyphorbol which are highly inflammatory but weakly promoting showed the same low potency in 3T3 cells as in chick embryo fibroblasts. These results suggest that 3T3 cells and chick embryo fibroblasts have homologous targets for the phorbol related diterpene esters. All phorbol related diterpene esters were of comparable efficacy in the 3T3 system with the exception of 4-O-methylphorbol 12-myristate 13-acetate. The lower efficacy of 4-O-methylphorbol 12-myristate 13-acetate may help account for its inactivity as a tumor promoter.

• Authors: W G Dunphy, C C Lau, P M Blumberg
• Journal: Carcinogenesis (Carcinogenesis) Vol. 1 Issue 4 Pg. 347-51 (Apr 1980) ISSN: 0143-3334 [Print] England
• PMID: 7273274 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Diterpenes
• Phorbol Esters
• Phorbols
• 4-O-methyl-12-O-tetradecanoylphorbol 13-acetate
• Deoxyglucose
• Tetradecanoylphorbol Acetate

Topics

• Animals
• Cells, Cultured
• Chick Embryo
• Deoxyglucose (metabolism)
• Diterpenes (pharmacology)
• Fibroblasts (drug effects)
• Mice
• Phorbol Esters (pharmacology)
• Phorbols (pharmacology)
• Structure-Activity Relationship
• Tetradecanoylphorbol Acetate (analogs & derivatives, pharmacology)