Normal cells abide by strict biological schedules – that is, they grow, divide, and die at regular intervals according to the body’s circadian clock. For cancer cells, however, this clock is malfunctioned and cancer seems to spend more time growing and dividing than they do dying. Now, for the first time, researchers demonstrate that resetting these malfunctioned clocks in cancer can slow its proliferation.
All animals have a built-in circadian rhythm – a biological cycle that responds to environmental stimuli. When this cycle is disrupted, such as by exposure to stress or different conditions, the body’s cells are also thrown off-kiltered. In the long-term, scientists have linked these alterations with higher risks for cancer.
If dysregulation of the body’s biological clock promotes cancer activity, could tweaks to the same system restore balance and slow cancer progression? "There were indications suggesting that the malfunctioning clock contributed to rapid tumor growth, but this had never been demonstrated,” said Nicolas Cermakian, a professor in McGill University's Department of Psychiatry, and the study’s senior author.
Cermakian and colleagues set out to test this hypothesis in skin and colon cancer cells, as well as in mice. “Thanks to the use of a chemical or a thermic treatment, we succeeded in 'repairing' these cells' clock and restoring it to its normal functioning. In these conditions, tumor growth drops nearly in half," explains Cermakian.
“We found that clock genes were suppressed in B16 cells and tumors, but treatments inducing circadian rhythmicity, such as dexamethasone, forskolin and heat shock, triggered rhythmic clock and cell cycle gene expression, which resulted in fewer cells in S phase and more in G1 phase,” the article’s authors wrote. “Accordingly, B16 proliferation in vitro and tumor growth in vivo was slowed down.”
These results show that timekeeping can be a potent way to target cancer cells. Though done in cell culture and mice, the results offer hope that that resetting the circadian clock may also work in human cancers too.
"Activating the biological clock in tumors could become an innovative approach in slowing their growth or that of metastases. This would give people more time to use more conventional treatment modalities, such as surgery or chemotherapy," said Cermakian. It now remains to be shown that we can target the clocks in human tumors the same way."
Additional sources: McGill University