Low-dose 5-fluorouracil induces cell cycle G2 arrest and apoptosis in keloid fibroblasts.

Abstract

BACKGROUND:

Intralesional injection of low-dose 5-fluorouracil (5-FU) has recently been used as an experimental modality for treating keloid scarring and has shown promising efficacy in improving scar appearance and preventing recurrence of the keloid.

OBJECTIVES:

We sought to explore the cellular- and molecular-based evidence for the observed clinical benefits.

METHODS:

Primary cell lines of keloid fibroblasts were treated with 5-FU at a range of lower doses (∼10 mg mL(-1) ) in monolayer culture and subjected to examination for cell viability, proliferative potential, apoptosis, cell cycle and associated proteins involved in cell cycle control.

RESULTS:

5-FU significantly inhibited cell proliferation of keloid fibroblasts in the full dose range used in this study. The DNA synthesis was completely inhibited by 5-FU at 72 h, and significant cell apoptosis was observed at concentrations ≥ 1 mg mL(-1) for a period over 72 h. 5-FU caused a significant delay in cell cycle progression and the G2/M phase arrest. 5-FU induced p53 and p21 accumulation together with a decrease in cyclin B1 and Bcl-2 levels in treated keloid fibroblasts.

CONCLUSIONS:

Our data indicate that low-dose 5-FU (as low as 1 mg mL(-1) ) induces significant inhibition of proliferation, G2/M cell cycle arrest and apoptosis but not immediate cell death of keloid fibroblasts. The lack of tissue necrosis is a particular benefit as further scarring is likely to be prevented. These results support the use of low-dose 5-FU as a potential modality for treating keloid scars.

• Authors: L Huang, Y P Wong, Y J Cai, I Lung, C S Leung, A Burd
• Journal: The British journal of dermatology (Br J Dermatol) Vol. 163 Issue 6 Pg. 1181-5 (Dec 2010) ISSN: 1365-2133 [Electronic] England
• PMID: 20633010 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 The Authors. BJD © 2010 British Association of Dermatologists.

Chemical References

• Cell Cycle Proteins
• Immunosuppressive Agents
• Fluorouracil

Topics

• Adolescent
• Adult
• Apoptosis (drug effects)
• Cell Cycle (drug effects, physiology)
• Cell Cycle Proteins (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Child
• Enzyme-Linked Immunosorbent Assay
• Fibroblasts (drug effects)
• Fluorouracil (pharmacology)
• G2 Phase (physiology)
• Humans
• Immunosuppressive Agents (pharmacology)
• Injections, Intralesional
• Keloid (drug therapy, metabolism, pathology)
• Young Adult