Highlights
- •STS treatment can inhibit melanoma cell proliferation, viability, and EMT process.
- •STS inhibits melanoma development via releasing H2S.
- •STS inhibits the EMT process via downregulating the activity of the Wnt/β-catenin signaling pathway.
Abstract
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/β-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/β-catenin
signaling pathway. Mechanistically, we defined that STS inhibited the EMT process
via the Wnt/β-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/β-catenin signaling pathway,
which provides a new clue to treating melanoma.
Abbreviations:
DMEM (Dulbecco's modified Eagle's medium), RPMI 1640 (Roswell Park Memorial Institute 1640), FBS (fetal bovine serum), PVDF (polyvinylidene fluoride), TBST (Tris Buffered Saline Tween), EMT (Epithelial-to-mesenchymal transition), PBS (phosphate-buffered saline), STS (sodium thiosulfate), H2S (hydrogen sulfide), DAPI (4',6-Diamidino-2'-phenylindole)Keywords
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Article info
Publication history
Published online: February 14, 2023
Accepted:
February 8,
2023
Received in revised form:
January 3,
2023
Received:
July 1,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
