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  • Title: As4S4 Exhibits Good Killing Effect on Multiple Myeloma Cells Via Repressing SOCS1 Methylation-Mediated JAK2/STAT3 Signaling Pathway.
    Author: Wu D, Dong W, Fang K, Wang M.
    Journal: Technol Cancer Res Treat; 2019; 18():1533033819896806. PubMed ID: 31868118.
    Abstract:
    OBJECTIVE: This study aimed to investigate the effect of tetra-arsenic tetra-sulfide on treating multiple myeloma and its potential regulation on suppressor of cytokine signaling 1 methylation-mediated Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway. METHODS: Tetra-arsenic tetra-sulfide with different concentrations were used to treat U266 cells, and cell viability was measured at 12, 24, and 48 hours with 0 μM tetra-arsenic tetra-sulfide treatment as control by Cell Counting Kit-8 assay. Suppressor of cytokine signaling 1 methylation and expression were determined by methylation-specific polymerase chain reaction, quantitative polymerase chain reaction, and Western blot, respectively, in U266 cells and normal plasma cells and in U266 cells treated by tetra-arsenic tetra-sulfide. Then, rescue experiments were performed by transfecting suppressor of cytokine signaling 1 small interfering RNA into tetra-arsenic tetra-sulfide-treated U266 cells. Besides, phosphor-Janus kinase 2, Janus kinase 2, phospho-signal transducer and activator of transcription 3, and signal transducer and activator of transcription 3 expressions were determined by Western blot. RESULTS: Tetra-arsenic tetra-sulfide inhibited U266 cell viability efficiently in a dose- and time-dependent manner. Suppressor of cytokine signaling 1 methylation was higher while suppressor of cytokine signaling 1 expression was lower in U266 cells compared to normal plasma cells; when treated by tetra-arsenic tetra-sulfide, suppressor of cytokine signaling 1 methylation was decreased while suppressor of cytokine signaling 1 expression was increased in U266 cells, along with the reduced phospho-Janus kinase 2 and phospho-signal transducer and activator of transcription 3 expressions. Then, suppressor of cytokine signaling 1 small interfering RNA enhanced the cell viability and phospho-Janus kinase 2 as well as phospho-signal transducer and activator of transcription 3 expressions in both tetra-arsenic tetra-sulfide treatment-free and tetra-arsenic tetra-sulfide-treated U266 cells. CONCLUSION: Tetra-arsenic tetra-sulfide exhibits good killing effect on multiple myeloma cells via repressing suppressor of cytokine signaling 1 methylation and downstream Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway, which might serve as a potential treatment option for multiple myeloma.
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