Journal of dermatological science · 2025
Thiotaurine inhibits melanoma progression by enhancing Ca2+ overload-induced cellular apoptosis.
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Wang Di, Xie Ansheng, Luo Jialiang, Li Lei, Zhang Zhiwen, Deng Weiwei, Yang Bin, Chang Yuan, Liang Yunsheng
Аннотация
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.
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.