engleski

Antiproliferative effects of three newly synthetised compounds on the cell cultures from the patients with Dupuytren’ s contracture

Dupuytren’ s contracture (DC) Dupuytren’ s disease (DD) is a nodular palmar fibromatosis leading to flexion contractures of the fingers and loss of hand function. It is characterized by nodular fibroblastic proliferation and accumulation of myofibroblasts. Methods of treatment can be divided into conservative and operative, however high recurrence rates have not been solved by any means. Experimental chemotherapy, such as 5-fluorouracil (5-FU), proved to be useful in acting locally in the palm by inhibiting myofibroblasts proliferation. 5-FU was shown to inhibit both, proliferation and myofibroblast differentiation in DC’ s cell cultures. Therefore, we established primary fibroblasts/myofibroblasts cultures as a model for studying the effects of several newly synthesized chemical compounds on proliferation and differentiation of Dupuytren’ s fibroblasts/myofibrobalsts. Cells were characterized by MTT-proliferation assays and flow cytometric analysis of the cell cycle. Cells from the affected part (D) of fascia proliferated faster then the cells from non-affected part (ND). Also, the percentage of cells in the S-phase of the cell cycle was higher in the D than in the ND cells. The presence of myofibroblasts in culture was ascertained by immunocytochemistry and Western blot method, as we assed the quantity of α -smooth actin and p21 as markers for differentiated fibroblasts. We have further tested cytotoxic and antiproliferatve effects of 3 compounds (a N-sulfonylpyrimidine derivative, an amidino substituted benzimidazo(1, 2-a)quinoline derivative and an amido-substituted dithieno-kinolone derivative) by MTT-test and showed them all to have a strong antiproliferative effect on established cell lines.

Dupuytren's contracture; antiproliferative effect; primary cell cultures

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