Citation: Blask DE, Dauchy RT, Dauchy EM, Mao L, Hill SM, Greene MW, et al. (2014) Light Exposure at Night Disrupts Host/Cancer Circadian Regulatory Dynamics: Impact on the Warburg Effect, Lipid Signaling and Tumor Growth Prevention. PLoS ONE 9(8): e102776. https://doi.org/10.1371/journal.pone.0102776
Abstract
The central circadian clock within the suprachiasmatic nucleus (SCN) plays an important role in temporally organizing and coordinating many of the processes governing cancer cell proliferation and tumor growth in synchrony with the daily light/dark cycle which may contribute to endogenous cancer prevention. Bioenergetic substrates and molecular intermediates required for building tumor biomass each day are derived from both aerobic glycolysis (Warburg effect) and lipid metabolism. Using tissue-isolated human breast cancer xenografts grown in nude rats, we determined that circulating systemic factors in the host and the Warburg effect, linoleic acid uptake/metabolism and growth signaling activities in the tumor are dynamically regulated, coordinated and integrated within circadian time structure over a 24-hour light/dark cycle by SCN-driven nocturnal pineal production of the anticancer hormone melatonin. Dim light at night (LAN)-induced melatonin suppression disrupts this circadian-regulated host/cancer balance among several important cancer preventative signaling mechanisms, leading to hyperglycemia and hyperinsulinemia in the host and runaway aerobic glycolysis, lipid signaling and proliferative activity in the tumor.
Extract
The circadian organization and disruption of tumor metabolism revealed by our experiments, and their consequences for tumor growth, may represent a next generation hallmark of cancer with respect to cancer prevention [36]. Comprehensive knowledge of the circadian nature of tumor metabolic signaling mechanisms and proliferative activity in the context of the circadian control of whole-body metabolism, may be essential for the rational development of new preventative and therapeutic approaches directed at critical metabolic targets [37], [38] that oscillate predictably throughout the 24-hour day. Therefore, the success of metabolically-targeted preventative and therapeutic strategies may ultimately depend upon their optimal temporal coordination with host/cancer circadian timekeeping. Moreover, LEN-induced circadian disruption of the host/cancer metabolic balance may contribute to an increased breast cancer risk in women working night shifts [20], [39] who may also be predisposed to developing a spectrum of metabolic diseases such as type-2 diabetes, obesity and/or metabolic syndrome [18], [19] that may further exacerbate breast cancer risk, as well as, compromise efforts to treat and/or further prevent breast and other cancers.