ADT-OH exhibits anti-metastatic activity on malignant melanoma through inhibition of FAK/Paxillin signaling pathways

Background: Melanoma is a highly aggressive cancer, and its high metastasis results in a high lethality. Hydrogen sulfide (H2S) is now widely recognized as the third endogenous gas delivery substance and may play a key role in cancer biological processes. The present study was designed to evaluate the anti-metastatic effect of H2S-donor ADT-OH on melanoma cells and the underlying mechanism.Methods: Firstly, the effect of ADT-OH on the migration of melanoma cells was explored in vivo by the mouse footpad injection model and the mouse tail vein metastasis model. Tumor xenograft growth and tumor tissue H&E analyses were also measured in vivo. Then, the migration inhibitory effect and the underlying mechanism of ADT-OH on B16F10, B16F1 and A375 melanoma cell lines were evaluated by wound healing, transwell, western blot and immunofluorescence analyses. Results: Our data showed that ADT-OH inhibited the migration and invasion of melanoma cells significantly in vivo in three different animal models. Further research showed that ADT-OH significantly suppressed the migratory, invasive and adhesive properties of A375 and B16F10 cells as measured by the wound-healing and transwell assays. Mechanistically, ADT-OH treatment suppressed the EMT processes and reduced the enzymatic activity of FAK and Paxillin. Moreover, abnormal CSE/CBS and AKT signaling pathways in A375 and B16F10 cells were notably observed following ADT-OH treatment. Additionally, ADT-OH at higher concentration significantly inhibited the proliferation of highly metastatic melanoma A375 and B16F10 cells.Conclusions: Our results suggest that ADT-OH exerts anti-metastasis activity in melanoma cells by suppressing the EMT process through the CSE/CBS and FAK signaling pathways, and it might be used as an agent against metastatic melanoma in future.