5-Fluorouracil Selectively Inhibits Collagen Synthesis

Abstract

The clinical implication is that 5-fluorouracil could possibly reduce extracellular matrix production and therefore reduce recurrence of Dupuytren's disease of the hand.

The efficacy of single-dose 5-fluorouracil therapy in experimental caustic esophageal burn

“…Bulstrode et al [12] evaluated the effects of a single 5-minute exposure of different 5-FU concentrations on tendon fibroblasts and found that 5-FU caused a dose-dependent decrease in collagen synthesis, and this effect was maximal at a concentration of 25 mg/mL. Therefore, we used this concentration in the local treatment group.…”

“…Recent studies showed that a single dose of 5-FU is a very effective inhibitor of fibroblast proliferation and differentiation for prolonged periods [10,11]. The putative mechanism of 5-FU action, inhibition of thymidylate synthetase, and impairing function of nucleic acids would lead to a global inhibition of fibroblast function [12]. These observations have stimulated great interest in the potential benefits of this antimetabolite in fibrosis-related disorders.…”

“…This antimetabolite leads to DNA damage and cell death only in high doses [10]. At much lower doses, 5-FU has no cytotoxic effects but only decreases cellular metabolism and acts as a negative regulator of collagen synthesis, causing a significant reduction in collagen protein synthesis by fibroblasts [12]. It has also been shown that cells that are growth arrested by 5-FU at much lower doses are still capable of certain functions, such as migration and secretion, which give them the capacity to be involved in healing [4,11].…”

“…More recently, 5-FU has been shown to selectively reduce collagen type I synthesis [12]. Fibrosis mainly comprises collagen type I; therefore, selective inhibition of this type collagen synthesis would reduce stricture formation without affecting tissue structure.…”

Dupuytren's Disease: Review of the Current Literature

“…In their in vitro study, Rayan et al found that Verapmil and Nifidipine inhibits myofibroblast contraction, and thus may be useful in the early stages of the disease [28]. The use of 5-Fluorouracil has been found, in vitro , to cause a dose-dependent selective and specific decrease in collagen production by inhibition of fibroblast proliferation and myofibroblast differentiation [59]. The authors concluded that the clinical implication is that 5-fluorouracil could possibly reduce the recurrence of Dupuytren's disease in the hand.…”