Arsenic hexoxide has differential effects on cell proliferation and genome-wide gene expression in human primary mammary epithelial and MCF7 cells

作者: Stuart K Calderwood , Heeyoun Bunch , Keunsoo Kang , Dong-Hyung Cho , Na Yeon Park

DOI: 10.1101/2021.01.12.426459

关键词: DNA repairCell cycleCell typeTranscriptomeChemistryCancer cellCell cultureProgrammed cell deathCell biologyCell growth

摘要: Arsenic is reportedly a biphasic inorganic compound for its toxicity and anticancer effects in humans [1, 2]. Recent studies have shown that certain arsenic compounds including hexoxide (AS4O6; hereafter, AS6) induce programmed cell death cycle arrest human cancer cells murine models [3, 4]. However, the mechanisms by which AS6 suppresses are incompletely understood. In this study, we report of through transcriptome analyses. particular, cytotoxicity global gene expression regulation were compared normal breast epithelial cells. Using RNA-sequencing bioinformatics analyses, differentially expressed genes significantly affected biological pathways these types validated real-time quantitative polymerase chain reaction immunoblotting assays. Our data show markedly differential on mammary (HUMEC) Michigan Cancer Foundation 7 (MCF7), line. selectively arrests growth induces MCF7 without affecting HUMEC dose-dependent manner. alters transcription large number cells, but much fewer HUMEC. Importantly, found proliferation, cycle, DNA repair suppressed whereas cellular stress response apoptotic increase AS6-treated Together, provide first evidence cancerous suggesting at moderate concentrations apoptosis modulating genome-wide expression, leading to compromised increased genome instability

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