Multiple roles of arsenic compounds in phase separation and membraneless organelles formation determine their therapeutic efficacy in tumors

Arsenic compounds are widely used for the therapeutic intervention of multiple diseases. Ancient pharmacologists discovered the medicinal utility of these highly toxic substances, and modern pharmacologists have further recognized the specific active ingredients in human diseases. In particular, Arsenic trioxide (ATO), as a main component, has therapeutic effects on various tumors (including leukemia, hepatocellular carcinoma, lung cancer, etc.). However, its toxicity limits its efficacy, and controlling the toxicity has been an important issue. Interestingly, recent evidence has pointed out the pivotal roles of arsenic compounds in phase separation and membraneless organelles formation, which may determine their toxicity and therapeutic efficacy. Here, we summarize the arsenic compounds-regulating phase separation and membraneless organelles formation. We further hypothesize their potential involvement in the therapy and toxicity of arsenic compounds, highlighting potential mechanisms underlying the clinical application of arsenic compounds. [Display omitted] •ATO induces PML-RARa degradation and affects PML nuclear bodies.•Arsenite promotes nuclear speckles formation.•Arsenic compounds have dual roles in paraspeckles formation.•Arsenite brings out stress granules formation.•Arsenite facilitates processing body formation.