Thiotaurine inhibits melanoma progression by enhancing Ca2+ overload-induced cellular apoptosis.

BACKGROUND

Melanoma is the most dangerous type of skin cancer with poor therapy outcomes. Since malignant cells are more susceptible to Ca2+ overload than normal cells, activating Ca2+ overload-mediated apoptosis may be a promising strategy to inhibit melanoma progression. Hydrogen sulfide (H2S) donors can regulate Ca2+ channels, but their effects on melanoma cells remain unclear.

OBJECTIVE

To explore the effects of Thiotaurine (TTAU), an H2S donor, on melanoma cells and its underlying mechanisms.

METHODS

We tested the effect of TTAU by culturing melanoma cells in vitro and establishing the xenograft model of mice in vivo. Cell proliferation and apoptosis were assessed using the CCK-8 test and flow cytometry. Molecules involved in apoptosis or Ca2+-related signal transduction were analyzed by western blotting. Immunofluorescence was used to measure Ca2+ levels, mitochondrial damage, and reactive oxygen species (ROS).

RESULTS

TTAU significantly reduced melanoma cell viability and induced apoptosis both in vitro and in vivo. Mechanistically, TTAU increased intracellular Ca2+, upregulated transient receptor potential vanilloid 1(TRPV1), and decreased activating transcription factor 3(ATF3) by nuclear factor of activated T cell cytoplasmic 1(NFATc1). TTAU also caused mitochondrial damage and ROS overproduction, which also promoted apoptosis.

CONCLUSION

We first elucidate that TTAU inhibits melanoma progression by activating Ca2+ influx-NFATc1-ATF3 signaling and aggravating mitochondrial oxidative stress, in which TRPV1 may act as an amplifier for Ca2+ influx. Our research is expected to provide new ideas for the treatment of tumors such as melanoma, as well as the clinical application of reactive sulfur species-based drugs.