Sodium thiosulfate inhibits epithelial-mesenchymal transition in melanoma via regulating the Wnt/-catenin signaling pathway

Background: Melanoma is the most common form of skin cancer. Given its high metastasis and high recurrence, its therapies are constantly updated. Objective: The study aims to prove the efficacy of sodium thiosulfate (STS), an antidote to cyanide or nitroprusside poisoning, in melanoma treatment. Methods: We tested the effect of STS by culturing melanoma cells (B16 and A375) in vitro and establishing melanoma mouse models in vivo. The proliferation and viability of melanoma cells were measured by the CCK-8 test, cell cycle assay, apoptosis analysis, wound healing assay, and transwell migration assay. The expression of apoptosis-related molecules, epithelial-mesenchymal transition (EMT)-associated molecules, and the Wnt/beta-catenin signaling pathway-related molecules were determined by Western blotting and immunofluorescence. Results: The high metastasis of melanoma is considered to be linked to the EMT process. The scratch assay using B16 and A375 cells also showed that STS could inhibit the EMT process of melanoma. We demonstrated that STS inhibited the proliferation, viability, and EMT process of melanoma by releasing H2S. STS-mediated weakening of cell migration was related to the inhibition of the Wnt/beta-catenin signaling pathway. Mechanistically, we defined that STS inhibited the EMT process via the Wnt/beta-catenin signaling pathway. Conclusions: These results suggest that the negative effect of STS on melanoma development is mediated by the reduction of EMT via the regulation of the Wnt/beta-catenin signaling pathway, which provides a new clue to treating melanoma. (c) 2023 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.