The disruption of melatonin production during the night through light exposure reduces tumor latency and drives resistance to tamoxifen in a model of estrogen receptor positive alpha (ERa+) breast cancer.
Melatonin is an hormone mainly produced by the pineal gland in the brain and primarily regulates sleeping habits. Its production is light sensitive; therefore, it is produced only in complete darkness, and sleeping in synthetic lights can interfere with its production. Melatonin has also been involved in the regulation of reproduction, timing of ovulation, aging, immune function, and cancer1. In 2001 a study linked night shift rotation with a moderate increase in breast cancer risk2. Studies have shown that melatonin antagonizes the metabolism of linoleic acid, the most prevalent polyunsaturated fatty acid present in the Western diet that upregulates the expression of genes controlling ER expression, cell cycle, and growth.
A group led by Dr. Steven Hill at the Tulane University (Louisiana)3 investigated how disruption of melatonin production influences not only growth but also response to tamoxifen of ERa+ tumors implanted into rats (xenograft). They did two sets of experiments. In the first set they compared animals kept under normal conditions with animals kept under dim light exposure at night (dLEN); in the second set, they compared dLEN mice with dLEN mice supplemented with nighttime melatonin. They found that tumors implanted in the dLEN rats had a shorter latency and a 2.6-fold increase in the growth rate compared with the controls. These tumors were also totally resistant to tamoxifen, whereas the control animals responded to the therapy. The dLED tumors showed high levels of proliferative markers, increased metabolism, and low apoptosis. Strikingly, when the nighttime melatonin was supplemented in the dLEN mice, tumor growth latency was reduced and resistance to tamoxifen was reestablished, with reduction of metabolism, proliferation markers, and increase in apoptosis.
Many studies have shown that melatonin can affect tumor growth in different cancer models, but this is the first study involving melatonin in resistance to therapy. The resistance to tamoxifen is a big problem in the treatment of ER+ breast cancer; about 30% of patients show resistance, and the causes are not totally understood. Strikingly, this research indicates that melatonin disruption affects resistance to therapy, through a molecular mechanism that may involve ER phosphorylation. Several lifestyle habits can influence cancer risk, cancer development, and resistance to therapy—e.g. diet, smoking, exercise. In addition, this report indicates that even sleeping in the darkness might be more beneficial against cancer.
Sleep in the dark!
1Melatonin, sleep disturbance and cancer risk. Blask DE.Sleep Med Rev. 2009 Aug;13(4):257-64. doi: 10.1016/j.smrv.2008.07.007. Epub 2008 Dec 17. Review.
2Rotating night shifts and risk of breast cancer in women participating in the nurses’ health study.Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, Colditz GA.J Natl Cancer Inst. 2001 Oct 17;93(20):1563-8.
3Circadian and melatonin disruption by exposure to light at night drives intrinsic resistance to tamoxifen therapy in breast cancer. Dauchy RT, Xiang S, Mao L, Brimer S, Wren MA, Yuan L, Anbalagan M, Hauch A, Frasch T, Rowan BG, Blask DE, Hill SM. Cancer Res. 2014 Aug 1;74(15):4099-110. doi: 10.1158/0008-5472.CAN-13-3156.