Circadian clocks are fundamental, time-tracking systems that allow organisms to adapt to the time of day, and drive many cellular processes, including proliferation and metabolism. Epidemiological evidence has shown that alteration of circadian rhythms via night-shift work, chronic jet lag, or other conditioning, leads to increased susceptibility to cancers, worse patient prognoses, and drug resistance during cancer treatment. While it is unclear how circadian rhythms are altered in cancer, one of our approaches toward understanding this connection is via use of small molecules. We used several compounds to modulate circadian periods in an osteosarcoma cell line (U2OS) and assessed their resulting effects on oncogenic behaviors. Luciferase reporters, whose expression were driven via Bmal1 and Per2 (positive and negative protein components of the core clock), were generated to facilitate the visualization and quantitative analysis of circadian oscillations. The molecules employed target proteins that either directly or indirectly involved in circadian regulatory pathways. We show that we are able to increase or decrease the circadian periods of Bmal1 and Per2 in a dose-dependent manner, and can also affect the properties of the cells, including their proliferation and motility.

Small molecule modulation of circadian rhythms in cancer cells

2019 Fall National Meeting

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