IMAGE: Circadian dysregulation of the cell cycle increases tumor growth and time-dependent anti-cancer activity of PD-0332991. view more
Credit: Amita Sehgal
Disrupting normal circadian rhythms promotes tumor growth and suppresses the effects of a tumor-fighting drug, according to a new study publishing April 30 in the open-access journal PLOS Biology by Yool Lee, Amita Sehgal, and colleagues at the University of Pennsylvania. The results provide mechanistic support for “chronotherapy,” the delivery of cancer drugs timed to the endogenous circadian rhythm.
Circadian rhythms regulate many aspects of physiology from the organismic to the subcellular levels. Disruption of circadian rhythms, whether through jet travel, shift work, or sleep disturbances, is a known risk factor for several types of cancer. In animal models, hormonally induced circadian disruption promotes tumor growth, but the underlying mechanism or mechanisms have not been clear.
To uncover potential mechanisms, the authors used the hormone dexamethasone to chronically advance daily rhythms in cultured cells. They found that treatment altered expression of multiple genes, especially those involved in regulating the cell cycle. Circadian rhythm disruption increased cell proliferation, an effect that could be traced to increased expression of a cell-cycle control protein called cyclin D1. Cyclin D1, in turn,
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