Light pollution, melatonin suppression and cancer growth

Light pollution, melatonin suppression and cancer growth

Author(s): Reiter RJ, Gultekin F, Manchester LC, Tan DX
Source: JOURNAL OF PINEAL RESEARCH Volume: 40 Issue: 4 Pages: 357-358 Published: MAY 2006

Article Text
The naturally occurring daily periods of light and darkness are an important source of internal order as manifested by the circadian rhythmicity exhibited by numerous organismal functions. Alterations of these daily fluctuations, referred to as chronodisruption [1], may be consequential in a number disorders, e.g. 'jet lag' [2], and diseases, e.g. cancer [3–5]. Given that the light:dark cycle is a central factor in circadian regulation, light during the normal dark period (light pollution), is becoming an increasing greater problem as societies become progressively more electrofied. Interruption of the daily dark period may have both subtle and not-so-subtle consequences in terms of human health.

One cycle that is quickly disturbed by light pollution is the pineal and blood melatonin rhythms. The repeated suppression of melatonin by light at night is a condition in which the health consequences may not be at all subtle. This is emphasized by the recent observations of Blask et al. [6] who, after a series of clever experiments, provided a highly plausible mechanism to explain how light suppression of melatonin at night accelerates the metabolic activity and growth of rat hepatoma and human MCF-7 cancer cells. The significance of these findings is reinforced by the earlier epidemiological studies in which the authors claimed that the repeated exposure of women to light at night, e.g. individuals who worked the night shift, had an increased incidence of breast [3,5,7] and colorectal cancer [8].

After transplantation of human MCF-7 cancer cells into nude rats, Blask et al. [6] showed that flooding the tumors with melatonin-deficient blood collected from premenopausal women during the day was inconsequential in terms of inhibiting cancer metabolism and growth. Conversely, melatonin-rich blood collected from the same women at night shut down the uptake and metabolism of the tumor growth promoter, linoleic acid, as well as the proliferation of the cancer cells. The most interesting aspect of the study, however, was that when the female blood donors were exposed to bright light at night to reduce endogenous melatonin levels, their blood was then incapable of inhibiting the cancer cells. Thus, light suppression of physiological melatonin levels negated the ability of the blood to limit tumor linoleic acid metabolism and cellular proliferation.

In the words of Blask, 'physiological nighttime levels of melatonin put tumors to sleep at night' while during the day when melatonin concentrations are normally low there are no limitations on their growth. Blask also is quoted as drawing the analogy that during light exposure at night tumors become 'insomniacs' [9].

There may be factors in addition to reducing linoleic acid uptake and metabolism that may be operative when melatonin, at physiological levels, limits growth of MCF-7 human cancer cells [10]. Leon-Blanco et al. [11] showed that melatonin also inhibits telomerase activity in MCF-7 cells. The activity of this enzyme is typically highly elevated in cancer cells [12] where it maintains the integrity and length of the telomeres of eukaryotic chromosomes. In noncancer cells, the telomeres gradually shorten over time making the chromosomes less stable and vulnerable to damage; this increases the propensity of normal cells to die. In cancer cells, the chromosomes remain durable because of the elevated telomerase activity so the cells are also more sturdy and resistant to death. When nude mice bearing MCF-7 tumors were treated with melatonin in their drinking water, not only was the growth of these tumors reduced but also telomerase activity as well as the levels of the mRNA of its catalytic submit, TERT, were also suppressed in the tumors. Moreover, like Blask et al. [6], Leon-Blanco et al. [11] reported that physiological concentrations of nighttime blood melatonin levels (about 1 nM) shut down telomerase activity of MCF-7 cancer cells. Thus, the ability of physiological levels of melatonin to 'put cancers to sleep at night' [9] extends not only to linoleic acid uptake and metabolism but to telomerase activity as well. Telomerase activity has been targeted as a site for cancer inhibition by the pharmaceutical industry [13].

These findings have additional important implications. Blask et al [6] noted that a 15–25% reduction in nocturnal melatonin levels is sufficient to promote tumor growth. This being the case, the age-related reduction in endogenous melatonin levels (which often exceeds 25%) [14] would be expected to increase the vulnerability of humans to cancer growth. As cancer is an age-related disease, the reduction of melatonin may be significant in mediating accelerated tumor growth in the elderly.

Finally, the amplitude of the nocturnal melatonin rhythm is determined by a variety of factors [15] and there are individuals who have a genetically attenuated nighttime melatonin rise. Given the high fidelity of the melatonin cycle over time, it is possible that these relatively melatonin-depressed humans are more susceptible to aggressive tumor metabolism and growth. These are considerations to ponder for future studies.