title: Daytime Blue Light Enhances the Nighttime Circadian Melatonin Inhibition of Human Prostate Cancer Growth.
abstract: Light controls pineal melatonin production and temporally coordinates circadian rhythms of metabolism and physiology in normal and neoplastic tissues. We previously showed that peak circulating nocturnal melatonin levels were 7-fold higher after daytime spectral transmittance of white light through blue-tinted (compared with clear) rodent cages. Here, we tested the hypothesis that daytime blue-light amplification of nocturnal melatonin enhances the inhibition of metabolism, signaling activity, and growth of prostate cancer xenografts. Compared with male nude rats housed in clear cages under a 12:12-h light:dark cycle, rats in blue-tinted cages (with increased transmittance of 462-484 nm and decreased red light greater than 640 nm) evinced over 6-fold higher peak plasma melatonin levels at middark phase (time, 2400), whereas midlight-phase levels (1200) were low (less than 3 pg/mL) in both groups. Circadian rhythms of arterial plasma levels of linoleic acid, glucose, lactic acid, pO2, pCO2, insulin, leptin, and corticosterone were disrupted in rats in blue cages as compared with the corresponding entrained rhythms in clear-caged rats. After implantation with tissue-isolated PC3 human prostate cancer xenografts, tumor latency-to-onset of growth and growth rates were markedly delayed, and tumor cAMP levels, uptake-metabolism of linoleic acid, aerobic glycolysis (Warburg effect), and growth signaling activities were reduced in rats in blue compared with clear cages. These data show that the amplification of nighttime melatonin levels by exposing nude rats to blue light during the daytime significantly reduces human prostate cancer metabolic, signaling, and proliferative activities.
authors.affiliation: Department of Structural and Cellular Biology, Tulane University School of Medicine, Tulane, Louisiana, USA. rdauchy@tulane.edu.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Dauchy
authors.affiliation: Department of Epidemiology, Tulane University School of Medicine, Tulane, Louisiana, USA.
authors.forename: Aaron E
authors.initials: AE
authors.lastname: Hoffman
authors.affiliation: Department of Structural and Cellular Biology, Tulane University School of Medicine, Tulane, Louisiana, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Wren-Dail
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Hanifin
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Warfield
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: George C
authors.initials: GC
authors.lastname: Brainard
authors.affiliation: Department of Structural and Cellular Biology, Tulane University School of Medicine, Tulane, Louisiana, USA.
authors.forename: Shulin
authors.initials: S
authors.lastname: Xiang
authors.affiliation: Department of Structural and Cellular Biology, Tulane University School of Medicine, Tulane, Louisiana, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Structural and Cellular Biology, Tulane University School of Medicine, Tulane, Louisiana, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Hill
authors.affiliation: Department of Structural and Cellular Biology, Tulane University School of Medicine, Tulane, Louisiana, USA.
authors.forename: Victoria P
authors.initials: VP
authors.lastname: Belancio
authors.affiliation: Department of Structural and Cellular Biology, Tulane University School of Medicine, Tulane, Louisiana, USA.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Dauchy
authors.affiliation: Department of Structural and Cellular Biology, Tulane University School of Medicine, Tulane, Louisiana, USA.
authors.forename: Kara
authors.initials: K
authors.lastname: Smith
authors.affiliation: Department of Structural and Cellular Biology, Tulane University School of Medicine, Tulane, Louisiana, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Blask
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002455:Cell Division / Q000502:physiology*; D002940:Circadian Rhythm; D003345:Corticosterone / Q000097:blood; D005227:Fatty Acids / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D020738:Leptin / Q000097:blood; D008027:Light; D008297:Male; D008550:Melatonin / Q000097:blood / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D051381:Rats; D011923:Rats, Nude
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids; D007328:Insulin; D020738:Leptin; D019344:Lactic Acid; D008550:Melatonin; D003345:Corticosterone