Lycorine Inhibits Hypertrophic Scar Formation by Inducing ROS-Mediated Apoptosis

Background: Hypertrophic scar (HS) is a fibrotic cutaneous disease with few effective therapies. Lycorine is a drug with pro-apoptotic ability and anti-fibrosis potential. This study aimed to test whether lycorine could trigger the Apoptosis of hypertrophic scar fibroblasts (HSFs) to inhibit HS formation. Methods: The proapoptotic and anti-fibrosis effects of lycorine on the viability and Apoptosis of human primary HSFs and their Reactive Oxygen Species (ROS) production as well as a rabbit ear model of HS were determined by CCK-8, flow cytometry, Western blot, immunofluorescence, transwell migration, Collagen gel contraction assays. Results: Lycorine treatment selectively decreased the viability of HSFs, and induced their Apoptosis, but not normal fibroblasts (NFs). Lycorine treatment increased the relative levels of Bax and cleaved PARP expression, cytochrome C cytoplasm translocation, but decreased Bcl-2, Caspase-3 and caspase-9 expression, the mitochondrial membrane potential (MMP) in HSFs. Lycorine inhibited the migration and contraction of HSFs, and reduced the expression of Collagen I, Collagen III and α-SMA. Mechanistically, lycorine treatment stimulated high levels of ROS production, leading to Apoptosis of HSFs while treatment with NAC, a ROS inhibitor, significantly mitigated or abrogated the pro-apoptotic and antifibrotic activity of lycorine in HSFs. Moreover, lycorine treatment mitigated the severity of HS in rabbit ears by inducing fibroblast Apoptosis. Conclusion: These results indicate that lycorine has a potent anti-fibrotic activity and is a potential drug for intervention of HS.

apoptosis; fibrosis; hypertrophic scar; lycorine; reactive oxygen species.