engleski

Screening of potential prodrugs on cells derived from Dupuytren’s disease patients

Dupuytren’s Disease (DD) is a fibroproliferative disorder, the cure for which is still limited to surgical excision of the affected fascia, often leading to high recurrence rates. Due to this fact, non-surgical treatments are being investigated, among them those targeting molecular processes of proliferation and differentiation in Dupuytren’ s cell cultures. Drugs with antiproliferative action may be valuable in DD treatment. Through characterization of changes on DD-specific cells, we therefore decided to test the therapeutic potential of new cytostatic drugs for DD treatment and/or for reduction of post-operative recurrence rates. The N-sulphonylpyrimidine derivative, amidino-substituted benzimidazo[1, 2-a]quinoline, and amidino dihydrothienothienyl[2, 3-c]quinolone hydrochloride, known to affect proliferation processes, were tested for their antiproliferative activity on primary fibroblasts/myofibroblasts cell cultures derived from the palmar fascia of patients with DD. Only amidino dihydrothienothienyl[2, 3-c]quinolone hydrochloride acted in a highly specific manner on cells derived from diseased fascia of DD patients and exhibited a low cytotoxic effect. This result might be a consequence of its specific activity on cytoskeleton changes occurring in differentiating cells. A similar short-term differential antiproliferative effect was observed by the N-sulphonylpyrimidine derivative that was however completely lost after 6- and 14-day treatments. The amidino-substituted benzimidazo[1, 2-a]quinoline exerted a strong non-specific, dose-related antiproliferative activity on cell types.

Dupuytren's contracture ; fibroblasts ; myofibroblasts

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