Halofuginone: an inhibitor of collagen type I synthesis

Biochim Biophys Acta. 1993 Feb 13;1156(2):107-12. doi: 10.1016/0304-4165(93)90123-p.


The effect of halofuginone--a plant alkaloid used as a coccidiostat in birds--on collagen metabolism was studied in various avian and mammalian cell cultures. In avian skin fibroblasts halofuginone attenuated the incorporation of [3H]proline into collagenase-digestible proteins (CDP) at concentrations as low as 10(-11) M, without affecting production of [3H]collagenase-nondigestible proteins (NCDP), cell proliferation or collagen degradation. Halofuginone depressed specifically the expression of alpha 1 gene of collagen type I but not that of collagen type II. This was demonstrated in skin fibroblasts and growth-plate chondrocytes using probes containing inserts sequences corresponding to the alpha 1(I) and alpha 1(II) mRNAs. A slight inhibition of the expression of alpha 2(I) was observed in avian skin fibroblasts but not in growth-plate chondrocytes. The inhibition of gene expression of both polypeptides of collagen type I in skin fibroblasts resulted in a decrease in synthesis, as demonstrated by immunoprecipitation with specific type I collagen antiserum. In primary cultures of mouse skin fibroblasts, avian epiphyseal growth plate chondrocytes and a rat embryo cell line--all of which produce and secrete collagen type I--halofuginone inhibited the incorporation of [3H]proline into CDP, the Rat-1 line being the most sensitive to the drug. These results suggest that halofuginone affects specifically type I collagen synthesis by repressing gene-expression. The need for extremely low concentrations of halofuginone to inhibit collagen type I synthesis, regardless of the tissue or animal species, contributes to the potential usefulness of the substance in studying collagen metabolism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Birds
  • Cell Division / drug effects
  • Cells, Cultured / drug effects
  • Coccidiostats / pharmacology*
  • Collagen / biosynthesis*
  • Collagen / genetics
  • Embryo, Mammalian
  • Embryo, Nonmammalian
  • Fibroblasts
  • Gene Expression / drug effects
  • Growth Plate
  • Matrix Metalloproteinase Inhibitors
  • Mice
  • Piperidines
  • Proline
  • Quinazolines / pharmacology*
  • Quinazolinones
  • Rats
  • Species Specificity


  • Coccidiostats
  • Matrix Metalloproteinase Inhibitors
  • Piperidines
  • Quinazolines
  • Quinazolinones
  • Collagen
  • Proline
  • halofuginone