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Light
during darkness, melatonin suppression and cancer progression
Blask
DE, Dauchy RT, Sauer LA, Krause JA, Brainard GC
Laboratory
of Experimental Neuroendocrinology/Oncology, Bassett Research Institute,
Cooperstown, NY 13326, USA.
david.blask@bassett.org
Over the
past few years, we have shown that the surge of melatonin in the circulation
during darkness represents a potent oncostatic signal to tissue-isolated rat
hepatoma 7288CTC, which is an ER+ adenocarcinoma of the liver.
This oncostatic effect occurs via a melatonin receptor-mediated suppression of
tumor cAMP production that leads to a suppression of the tumor uptake of
linoleic acid (LA), an essential fatty acid with substantial oncogenic
properties.
The ability of LA to promote cancer progression is accomplished by its
intracellular metabolism to 13-hydroxyoctadecadienoic acid (13-HODE) which
amplifies the activity of the epidermal growth factor receptor/mitogen-activated
protein kinase pathway leading to cell proliferation.
By blocking tumor LA uptake, melatonin effectively blocks the production of
13-HODE and thus, markedly attenuates tumor growth.
A similar effect of melatonin is observed in tissue-isolated, ER+ MCF-7 human
breast cancer xenografts and nitrosomethylurea (NMU)-induced rat mammary
cancers.
When male rats bearing tissue-isolated hepatomas are exposed either to constant
bright light (300 lux) or dim light (0.25 lux) during the dark phase of a
12L:12D photoperiod, the latency to onset was significantly reduced while the
growth of tumors was markedly increased over a 4 wk period as compared with
control tumors in 12L:12D-exposed rats.
In constant light- and dim light during darkness-exposed rats, melatonin levels
were completely suppressed while tumor growth, LA uptake and 13-HODE production
were markedly increased.
Similar results were obtained in constant bright light-exposed female rats
bearing tissue-isolated NMU-induced mammary cancers or MCF-7 human breast cancer
xenografts.
To date, these studies provide the most definitive experimental evidence that
light exposure during darkness increases the risk of cancer progression via
elimination of the nocturnal melatonin signal and its suppression of tumor LA
uptake and metabolism to 13-HODE.
PMID:
12163849 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12163849&dopt=Abstract
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