Ellagic acid inhibits the formation of hypertrophic scars by suppressing TGF-ß/Smad signaling pathway activity.

Hypertrophic scar (HS) is a benign fibroproliferative skin disease, which lacks the ideal treatment and drugs. Ellagic acid (EA) is a natural polyphenol that prevents fibroblasts from proliferating and migrating. This study aimed to determine the role of EA in HS formation and its possible mechanism by in vitro experiments. HS fibroblasts (HSFs) and normal fibroblasts (NFs) were separated from HS tissue and normal skin tissue, respectively. HSFs were treated with 10 and 50 µM EA to assess their effect on HS formation. In particular, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and scratch assay were used to detect the viability and migration ability of HSFs. Quantitative reverse transcriptase real-time polymerase chain reaction was used to measure the mRNA expression level of basic fibroblast growth factor (bFGF), extracellular matrix (ECM)-related gene collagen-I (COL-I), and fibronectin 1 (FN1) in HSFs. Finally, Western blot was utilized to measure the expression level of TGF-ß/Smad signaling pathway-related proteins in HSFs. The viability of HSFs was significantly increased compared with NFs. 10 and 50 µM EA treatment markedly inhibition the cell viability and migration of HSFs. EA treatment upregulated the bFGF expression level and downregulated the COL-I and FN1 expression level in HSFs. In addition, p-Smad2, p-Smad3, and transforming growth factor (TGF)-ß1 expression levels as well as p-Smad2/Smad2 and p-Smad3/Smad3 ratios remarkably decreased in HSFs after EA treatment. EA inhibited the formation of HSs by suppressing the viability and migration of HSFs and ECM deposition as well as by preventing the activation of TGF-ß/Smad signaling.

Cucurbitacin E inhibits cellular proliferation and induces apoptosis in melanoma by suppressing HSDL2 expression.

BACKGROUND: Melanoma is among the most aggressive types of skin malignancy and can have an unpredictable clinical course. Exploration of novel therapeutic targets and their regulators remains essential for the prevention and treatment of melanoma. METHODS: HSDL2 protein levels were examined by immunohistochemistry. The roles of HSDL2 in cell proliferation and apoptosis were identified by CCK-8 and colony formation assays. The function of HSDL2 in cell apoptosis was analysed by flow cytometry. Western blotting, cell proliferation and apoptosis and a xenograft tumour model were utilized to explore the inhibitory functions and mechanisms of CuE in melanoma. RESULTS: HSDL2 is overexpressed in melanoma and promotes melanoma progression by activating the ERK and AKT pathways. CuE could inhibit the ERK and AKT pathways by decreasing HSDL2 expression; therefore, CuE could inhibit melanoma growth in vitro and in vivo. CONCLUSION: HSDL2 may be a promising therapeutic target against melanoma, and CuE can inhibit melanoma by downregulating HSDL2 expression.