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• W2944998404 abstract "ABSTRACT Circadian rhythms are essential for controlling the cell cycle, cellular proliferation, and apoptosis, and hence, are tightly linked to cell fate. Disruption of circadian rhythms has been shown to trigger various pathological developments, including cancer. Several recent studies have used a variety of small molecules to affect circadian oscillations, however, their concomitant cellular effects were not assessed. Here, we use five molecules, grouped into direct versus indirect effectors of the circadian clock, to modulate periods in a human osteosarcoma cell line (U2OS), and determined their influences on cellular behaviors, including motility and colony formation. Luciferase reporters, whose expression were driven via Bmal1 - and Per2 -promoters (positive and negative protein components of the core clock), were used to facilitate the visualization and quantitative analysis of circadian oscillations. We show that all molecules significantly increase or decrease the circadian periods of Bmal1 and Per2 in a dose-dependent manner, but period length does not correlate with the extent of cell migration or proliferation. We observed that only molecules that affected circadian oscillations to a greater extent showed significant influence on cell functions (e.g. motility and colony formation). Because it is important to consider the likelihood of biological effects resulting from non-circadian targets, we also provide a thorough discussion of potential modes of action. Future studies should employ additional compounds that directly target circadian proteins and/or have different circadian effects, and evaluation in other cancer models to determine whether results obtained here remain consistent. For Table of Contents Only" @default.
• W2944998404 created "2019-05-29" @default.
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• W2944998404 date "2019-05-22" @default.
• W2944998404 modified "2023-09-23" @default.
• W2944998404 title "Oncogenic and Circadian Effects of Small Molecules Directly and Indirectly Targeting the Core Circadian Clock" @default.
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• W2944998404 doi "https://doi.org/10.1101/645861" @default.
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