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.