C. Heilmann et al., Effect of the cytostatic agent idarubicin on fibroblasts of the human Tenon's capsule compared with mitomycin C, BR J OPHTH, 83(8), 1999, pp. 961-966
Background/aims-To investigate the in vitro effect of a short time exposure
to the anthracycline idarubicin on proliferation, protein synthesis, and m
otility of human Tenon's capsule fibroblasts in comparison with the antitum
our antibiotic mitomycin C.
Methods-After determination of effective concentrations of idarubicin, fibr
oblasts of the human Tenon's capsule were exposed to idarubicin or mitomyci
n C at concentrations ranging from 0.1 mu g/ml to 1 mu g/ml or from 2.5 mu
g/ml to 250 mu g/ml, respectively, for 0.5, 2, or 5 minutes and cultured fo
r 60 days. Cell death by apoptosis caused by idarubicin treatment was confi
rmed by Hoechst 33258 staining. Further proliferation was explored by cell
counting and by H-3-thymidine uptake. Protein synthesis was measured by H-3
-proline uptake and motility was assessed by agarose droplet motility assay
.
Results-Idarubicin is able to exert toxicity and to induce apoptosis during
a short time exposure of 0.5 minutes at concentrations of 0.3-1 mu g/ml re
sulting in a significant reduction in cell number compared with the control
after 60 days. For mitomycin C, higher concentrations and longer expositio
ns were necessary. Even after treatment with 1 mu g/ml idarubicin or 250 mu
g/ml mitomycin C a few cells were able to incorporate H-3-thymidine. H-3-p
roline uptake up to 10 days after exposure to 0.3 mu g/ml idarubicin was fo
und not to be decreased. Cell motility was reduced after treatment with 1 m
u g/ml idarubicin for 5 minutes or with 250 mu g/ml mitomycin C for 2 or 5
minutes. For low mitomycin C concentrations, an increase in motility was fo
und during the first 10 days.
Conclusion-Idarubicin reduces proliferation of human Tenons's capsule fibro
blasts after incubation for 0.5 minutes at concentrations as low as 0.3-1 m
u g/ml. In comparison, mitomycin C requires longer exposure times and highe
r doses for equal results. Therefore, idarubicin may be useful in the preve
ntion of glaucoma filtering surgery failure.