Light exposure at night disrupts host/cancer circadian regulatory dynamics: impact on the Warburg effect, lipid signaling and tumor growth prevention

• Published in: PloS one 2014-08, Vol.9 (8), p.e102776-e102776
• Main Authors: Blask, David E, Dauchy, Robert T, Dauchy, Erin M, Mao, Lulu, Hill, Steven M, Greene, Michael W, Belancio, Victoria P, Sauer, Leonard A, Davidson, Leslie
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Bioenergetics; Biology and Life Sciences; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Breast Neoplasms - physiopathology; Breast Neoplasms - prevention & control; Cancer; Cell cycle; Cell division; Cell growth; Cell Line, Tumor; Cell Proliferation; Cellular biology; Circadian Rhythm; Circadian rhythms; Consortia; Deoxyribonucleic acid; DNA; Female; Glucose; Glucose metabolism; Glycolysis; Growth; Heterografts; Humans; Hyperglycemia; Hyperinsulinemia; Hypoxia; Insulin-like growth factors; Intermediates; Laboratories; Light; Linoleic acid; Lipid metabolism; Lipids; Medical research; Medicine; Medicine and Health Sciences; Melatonin; Melatonin - metabolism; Metabolism; Neoplasm Transplantation; Night; Oncology; Phosphorylation; Physiology; Pineal gland; Pineal Gland - metabolism; Pineal Gland - pathology; Pineal Gland - physiopathology; Prevention; Rats; Rats, Nude; Research and Analysis Methods; Signal transduction; Signaling; Substrates; Suprachiasmatic nucleus; Tumors; Unsaturated fatty acids; Xenografts; Xenotransplantation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0102776

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.