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PLoS One. 2014 Aug 6;9(8):e102776. doi: 10.1371/journal.pone.0102776. eCollection 2014.

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

Author information

1
Laboratory of Chrono-Neuroendocrine Oncology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America; Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America; Tulane Cancer Center and Louisiana Cancer Research Consortium, New Orleans, Louisiana, United States of America.
2
Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America; Tulane Cancer Center and Louisiana Cancer Research Consortium, New Orleans, Louisiana, United States of America.
3
Bassett Research Institute, Mary Imogene Bassett Hospital, Cooperstown, New York, United States of America.
4
Laboratory of Chrono-Neuroendocrine Oncology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.

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.

PMID:
25099274
PMCID:
PMC4123875
DOI:
10.1371/journal.pone.0102776
[Indexed for MEDLINE]
Free PMC Article

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