WASHINGTON -- Disruptions of one's circadian rhythm could lead to faster tumor growth, according to a new study published Tuesday in the journal PLOS Biology.
It has long been suggested that circadian disruptions, such as long-term night shift work, have multiple pathological consequences, but the underlying mechanisms had been largely unknown.
The new study, conducted by scientists from the University of Pennsylvania, showed that circadian disruptions trigger an increase in cell proliferation that, ultimately, shifts the cell-cycle balance and stimulates the growth of tumors in mice.
Researchers used the hormone dexamethasone to chronically advance daily rhythms in human cultured cells, mimicking frequent jet-lag.
They found that the treatment altered expression of multiple genes, most specifically activating CDK4/6 proteins. Excessive activity from these proteins is known to lead to increased cell division rates, and some cancer therapies work to directly inhibit CDK4/6 activity.
The findings also suggest that "chronotherapy" --the delivery of treatment timed to the host's circadian rhythm-- can improve the outcomes of drugs that inhibit tumor growth in mice.
Researchers found that one drug used for the treatment of breast cancer, Palbociclib, was more effective when taken in the morning than at night. Delivery of drug at a time of greater efficacy is expected to reduce the dose required, and thereby reduce side effects.
However, chronic circadian disruption reduced the efficacy of the therapy in human cultured cells, a finding that was validated in mice.
"Our findings strongly indicate that environmental or physiological disturbances of circadian rhythms such as shift work, abnormal sleep timing, or irregular psycho-sociological stresses can affect variability in both cancer growth and response to cancer drugs," said the study's first author Yool Lee, a research associate in the Sehgal Lab.
"Given this, it is reasonable to expect that resetting of the body clock by scheduled light-exposure, meal-times, or exercise, alongside a carefully timed chemotherapy regimen, would improve anti-tumor treatment," he added. (Xinhua)