Work

Engineered Nanoclusters to Selectively Reduce Mesenchymal and Epithelial Melanoma Cell Viability

Year: 2025

Type: article

Abstract: Melanoma is the most common type of skin cancer. Melanomas are well-known for their ability to metastasize to other organs, including the lungs, liver, brain, and bones. The ability of melanoma cells to switch among different phenotypes is a key mechanism that underscores their metastatic potential. We report here on the effect of calcium sulfide (CaS) dispersions in melanoma cells. Melanomas with the mesenchymal and epithelial phenotypes were observed during cell culture preparation. The dispersion reduced the relative percentage of melanomas with the mesenchymal and epithelial phenotypes to (55 + 5) and (57 + 5) %, respectively. In contrast, the viability of normal fibroblasts treated with the dispersion, or the reactants used to prepare the dispersion, remains nearly constant in the same period. Fluorescence imaging measurements are consistent with the release of cytochrome c from mitochondria and its translocation to the cell nuclei. The average expression of caspases 3 and 9 were found to be higher than in the corresponding melanoma control, consistent with intrinsic apoptosis. The response of vinculin expression was slightly different in types of cells. Vinculin was found to delocalize in the cytoplasm of treated mesenchymal melanoma cells with a slightly higher concentration at the end of the actin fibers. A statistically significant increase in the number of FAP in the edge of the cell membrane-external cellular matrix (ECM) was observed in post treated melanoma that exhibited the epithelial phenotype. The changes in vinculin expression and in the number of FAP are consistent with regulation of proteins associated with programmed cell death. It is proposed that the sulfides produced from the reactions of the nanoclusters in the acidic environment facilitate the regulation of proteins required to initiate apoptosis, although other processes may also be involved. Extension of the efforts to animal models will be an important step to the commercialization of the dispersion for melanoma treatment.

Source: Cancers

DOI: 10.3390/cancers17121903