Erianin inhibits cell migration and induces apoptosis by in-hibiting VEGF-α/PI3K/AKT signaling pathway in melanoma A375 cells

Abstract Erianin, extracted from Dendrobium chrysotoxum Lindl, has shown significant antitumour activity in various cancers, including bladder, cervical, and nasopharyngeal carcinoma. This study explores erianin's impact on melanoma, a prevalent intraocular malignancy in adults, emphasizing cell growth inhibition and its mechanism. Vascular endothelial growth factor-α (VEGF-α), a validated therapeutic target in melanoma angiogenesis, was considered. Despite its origin from Dendrobium plants in the Orchidaceae family, erianin's anti-melanoma effects and its potential to inhibit the PI3K/AKT/mTOR signalling pathway to decrease VEGF-α secretion in melanoma cells remain unexplored. Thus, erianin's effects on A375 cells and its underlying molecular mechanisms were investigated. Erianin induced apoptosis in A375 cells, as demonstrated by flow cytometry and western blot assays. Additionally, erianin inhibited A375 cell migration, proliferation, and invasion in vitro, evidenced by cell scratch, EdU stain, and transwell cell invasion assays. Mechanistically, erianin downregulated VEGF-α and VEGF Receptor 2 expression while inhibiting PI3K/AKT pathway activation, indicated by western blot and immunofluorescence analyses. Furthermore, both western blot and immunofluorescence analyses confirmed erianin's regulation of VEGF-α and VEGF-R2 expression. This study suggests that erianin is a novel compound capable of inducing cell apoptosis while suppressing the activation of the VEGF/PI3K/AKT signalling pathway in A375 cells, thereby inhibiting cell proliferation.