CYT997 Induces Apoptosis in Hypertrophic Scar Fibroblasts and Inhibits Scar Formation.

Abstract

Emerging evidence indicates that hypertrophic scars (HS) display tumor-like behaviors, characterized by excessive, rapid cellular proliferation. To investigate potential therapeutic interventions, this study focused on the effects of CYT997, a novel anti-cancer drug, on hypertrophic scar fibroblasts (HSFs). HS tissues were collected from patients and compared with normal skin samples. CYT997 decreased HSF viability in a concentration-dependent manner, with a selected concentration for further experiments. It selectively induced apoptosis in HSFs but not in normal fibroblasts, as shown by flow cytometry and fluorescence microscopy. CYT997 also reduced HSF migration, contractility, and expression of collagen I and α-smooth muscle actin (α-SMA), indicating decreased fibrosis. In a rabbit ear hypertrophic scar model, CYT997 treatment inhibited scar formation, reduced the scar elevation index, and promoted apoptosis in HSFs. It also regulated apoptosis-related proteins poly(ADP-ribose) polymerase (PARP) and caspase-3 in HSFs. These findings suggest that CYT997 has potential as a targeted therapy for hypertrophic scars by inducing apoptosis in HSFs and reducing fibrotic activity.