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Fast pH-Driven Solubilization Method of Realgar (As4S4) to Reduce the Toxicity of Arsenic [As(III)] for Medical Purposes

ABSTRACT: Acute promyelocytic leukemia (APL) is a fulminant form of hematological cancer, representing 5-15% of adult leukemias and also affecting children. It is characterized by the 15:17 chromosomal translocation, which produces the pathogenic retinoic acid receptor (RAR) alpha/promyelocytic leukemia protein (PML) fusion product. Remission of APL was recently achieved using the first chemotherapy-independent oral drug regimen in anticancer therapy, consisting of all-trans retinoic acid (targeting RARalpha) and the arsenic sulphide realgar (targeting PML). A broader use of realgar is, however, hampered by the poor solubility of this mineral. We here describe a scalable pH- and temperature-based solubilization process for realgar. The solution obtained displays higher therapeutic indices compared to other arseni-containing compounds, including opriment and arsenic trioxide (an intravenous chemotherapeutic counterpart), which is in line with the lower toxicity of realgar observed in clinical trials. Our data also show that solubilized realgar can disrupt HIV latency, the main barrier to an HIV/AIDS cure, in CD4 T cells of people living with HIV. This discovery may also open new avenues for designing therapies based on orally administrable arsenic-containing compounds.

ORGANISM(S): Homo sapiens

PROVIDER: GSE270992 | GEO | 2025/04/16

REPOSITORIES: GEO

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