What is the role of doxorubicin in the treatment of keloids and hypertrophic scars?

Updated: Jun 12, 2018
  • Author: Brian Berman, MD, PhD; Chief Editor: Dirk M Elston, MD  more...
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Answer

Doxorubicin (Adriamycin) is a commonly used chemotherapeutic agent that irreversibly inactivates prolyl 4-hydroxylase in human skin fibroblasts and has been shown to inhibit collagen alpha-chain assembly.

Sasaki et al showed through sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis that doxorubicin, at a clinically therapeutic concentration of 12.5 µm, inhibits the assembly of collagen triple-helical molecules. [27] SDS-PAGE analysis of control cultures showed a large fraction of [3H]proline-labeled procollagen polypeptides in triple-helical conformation; however, after the addition of doxorubicin at 12.5 µm, a very small amount of intact alpha-chains were found. These results suggest that the impaired wound healing observed in cancer patients who receive doxorubicin may result from the inhibition of prolyl 4-hydroxylase.

Another mechanism of doxorubicin-induced inhibition of collagen synthesis includes the inhibition of the enzyme prolidase, which is key in the process of collagen resynthesis, cleaving imidodipeptides containing C-terminal, and making proline available for its recycling and further generation of new collagen. Muszynska et al demonstrated this process in cultured human skin fibroblasts, also suggesting that this inhibition is a posttranslational event. [28, 29]

Other agents such as doxycycline, other nonsteroidal anti-inflammatory drugs (ie, acetylsalicylic acid, sodium salicylate, phenylbutazone, indomethacin), daunorubicin, gentamicin, netilmicin, anthracycline) [30] are also capable of inhibiting prolidase in cultured human skin fibroblasts. Further studies are warranted to determine if doxorubicin or any of the above-mentioned agents can be useful to treat patients with excessive scarring.


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