One of the chemicals responsible for helping establish the body’s circadian rhythms may also help doctors fight mesothelioma.
BMAL1 is an important component of the circadian clock, the internal biochemical ‘clock’ that regulates such important body functions as heart rhythm, wake-sleep cycles, and hunger. Previous studies have found that mesothelioma cells produce more BMAL1 than healthy cells. Now, a group of Japanese doctors is proposing that the extra BMAL1 in mesothelioma cells could serve as a target for anti-cancer drugs.
Malignant pleural mesothelioma – the most common form of mesothelioma – is a cancer of the mesothelial lining around the lungs. It is caused by exposure to asbestos and, to date, there is no consistently affective treatment. The irregular shape of mesothelioma tumors, their location so close to vital organs, and the fact that they tend to grow quickly make mesothelioma a challenge to treat. If a molecule could be ‘programmed’ to carry a drug into cells that overexpress BMAL1, it might be possible to destroy mesothelioma cells from the inside out while leaving nearby healthy cells intact.
To test the validity of their idea, the Japanese researchers exposed mesothelioma cell samples to a serum shock designed to disrupt normal circadian rhythms. In the healthy mesothelial cells, the shock caused a change in BMAL1 expression. But the mesothelioma cells continued to express extra BMAL1, suggesting that these cells do not follow same circadian rhythms as healthy cells.
When the researchers deliberately reduced the amount of BMAL1 in the mesothelioma cells, they observed cell cycle disruption and an increase in cell death. In fact, the depletion of BMAL1 caused a range of “drastic morphological changes”, including multiple nuclei, in the mesothelioma cells. The cells that contained the most BMAL1 were affected the most.
In a report on their findings in the International Journal of Cancer, the researchers conclude, “Taken together, these findings indicate that BMAL1 has a critical role in malignant pleural mesothelioma and could serve as an attractive therapeutic target for MPM (mesothelioma). “ Further study will be needed to confirm the findings.
Approximately 2,500 people are diagnosed with mesothelioma each year in the U.S.