Effect of the cytostatic agent idarubicin on fibroblasts of the human Tenon's capsule compared with mitomycin C.
OBJECTIVE
To investigate the in vitro effect of a short time exposure to the anthracycline idarubicin on proliferation, protein synthesis, and motility of human Tenon's capsule fibroblasts in comparison with the antitumour antibiotic mitomycin C.


METHODS
After determination of effective concentrations of idarubicin, fibroblasts of the human Tenon's capsule were exposed to idarubicin or mitomycin C at concentrations ranging from 0.1 microg/ml to 1 microg/ml or from 2.5 microg/ml to 250 microg/ml, respectively, for 0.5, 2, or 5 minutes and cultured for 60 days. Cell death by apoptosis caused by idarubicin treatment was confirmed by Hoechst 33258 staining. Further proliferation was explored by cell counting and by (3)H-thymidine uptake. Protein synthesis was measured by (3)H-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 microg/ml resulting in a significant reduction in cell number compared with the control after 60 days. For mitomycin C, higher concentrations and longer expositions were necessary. Even after treatment with 1 microg/ml idarubicin or 250 microg/ml mitomycin C a few cells were able to incorporate (3)H-thymidine. (3)H-proline uptake up to 10 days after exposure to 0.3 microg/ml idarubicin was found not to be decreased. Cell motility was reduced after treatment with 1 microg/ml idarubicin for 5 minutes or with 250 microg/ml mitomycin C for 2 or 5 minutes. For low mitomycin C concentrations, an increase in motility was found during the first 10 days.


CONCLUSIONS
Idarubicin reduces proliferation of human Tenons's capsule fibroblasts after incubation for 0.5 minutes at concentrations as low as 0.3-1 microg/ml. In comparison, mitomycin C requires longer exposure times and higher doses for equal results. Therefore, idarubicin may be useful in the prevention of glaucoma filtering surgery failure.
Department of Ophthalmology, Otto-von-Guericke-Universität Magdeburg, Germany.
C
C
Heilmann
P
P
Schönfeld
T
T
Schlüter
R
R
Bohnensack
W
W
Behrens-Baumann
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005205:Fascia / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018463:Filtering Surgery; D006801:Humans; D015255:Idarubicin / Q000494:pharmacology*; D016685:Mitomycin / Q000494:pharmacology*; D009801:Oculomotor Muscles / Q000166:cytology; D011392:Proline / Q000378:metabolism; D013285:Strabismus / Q000601:surgery; D013936:Thymidine / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D016685:Mitomycin; D011392:Proline; D013936:Thymidine; D015255:Idarubicin