Study of Arsenic Sulfide in Solid Tumor Cells Reveals Regulation of Nuclear Factors of Activated T-cells by PML and p53

Scientific Reports
Wenping DingSiyu Chen

Abstract

Arsenic sulfide (AS) has excellent cytotoxic activity in acute promyelocytic leukemia (APL) but its activity in solid tumors remains to be explored. Here we show that AS and cyclosporine A (CsA) exerted synergistic inhibitory effect on cell growth and c-Myc expression in HCT116 cells. AS inhibited the expression of PML, c-Myc, NFATc1, NFATc3, and NFATc4, while stimulating the expression of p53 and NFATc2. Knockdown of PML reduced NFATc1, NFATc2, NFATc3 and NFATc4 expression while overexpression of p53 stimulated NFATc2-luciferase activity that was further augmented by AS by binding to a set of p53 responsive elements (PREs) on the NFATc2 promoter. Additionally, overexpression of p53 suppressed NFATc3 and NFATc4. Reciprocally, NFATc3 knockdown enhanced p53 while reducing MDM2 expression indicating that NFATc3 is a negative regulator of p53 while a positive regulator of MDM2, consistent with its tumor-promoting property as knockdown of NFATc3 retarded cell growth in vitro and tumor growth in xenograft. In patients with colon cancer, tumor expression of NFATc2 correlated with superior survival, while nuclear NFATc1 with inferior survival. These results indicate that AS differentially regulates NFAT pathway through PML and p53 and ...Continue Reading

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Citations

Mar 8, 2017·Proceedings of the National Academy of Sciences of the United States of America·Elena KamyninaPatrick J Stover
Jan 25, 2020·Physical Chemistry Chemical Physics : PCCP·Vanesa Paula Cuenca-GotorFrancisco Javier Manjón
Nov 14, 2016·Archives of Toxicology·Karin EngströmKarin Broberg
Dec 12, 2019·Journal of Experimental & Clinical Cancer Research : CR·Ting KangSiyu Chen
Dec 14, 2018·Cancer Chemotherapy and Pharmacology·Shudan WangChaoying Li

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Methods Mentioned

BETA
acetylation
xenograft
ChIP
PCR
Protein Assay
transfect
fluorescence microscopy
transfection
immunoprecipitation
Assay

Software Mentioned

SPSS

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