The Journal of the National Cancer Institute published two papers reporting a significant increase in the risk of breast cancer among women who frequently did not sleep during the period of the night, 12am – 2am, when melatonin levels are typically at their highest. There was increased risk among women sleeping in the brightest bedrooms.
Moreover, women who had worked 30 and more years on rotating night shifts had a 36% greater risk of breast cancer compared with workers who had never worked nights.
Earlier, epidemiologists had shown an elevated breast cancer risk among post-menopausal radio and telegraph operators exposed to shift work as well as among flight attendants working markedly random night periods. ‘Melatonin hypothesis’ suggests that reduced pineal melatonin production might increase human breast cancer risk because a lower melatonin output would lead to an increase in the level of female sex hormones, and would stimulate proliferation of breast tissue.
Effect of Light Deprivation on Mammary Carcinogenesis
Kuralasov firstly studied the effect of light deprivation on growth and development of transplantable and DMBA-induced mammary tumors. Animals were kept in a dark room, or under a standard light-dark regimen. The transplantability of rat mammary carcinoma was 89.5% in rats kept at the standard light regimen and only 58.6% in rats under the constant darkness regimen. The average doubling time of the tumor growth was 82.3 h in the normal light group and 138 h in the constant dark group.
Administration of DMBA induced mammary adenocarcinomas in 49% of the normal light rats, and only in 5% of the constant darkness rats. The number of tumors per tumor-bearing rat was 3.15 for standard light group, and 1.01 in the constant darkness group. Survival of tumor-bearing rats in the constant dark group was 54.7% longer than that in the standard light group.
When started before maturity, the constant darkness regimen leads to acceleration of a maturation and to fast (in 4–8 weeks) development of the persistent estrus syndrome. In 15 weeks after the start of the exposure to constant light, follicular cysts in the ovaries were observed in 92% rats, whereas no cases of the ovarian cysts were observed in the standard light group.
Thus, experiments with rodents give evidence of the inhibitory effect of light deprivation on mammary carcinogenesis. There are some epidemiological data supporting these findings. Hahn showed that risk of breast carcinoma was two times less in primary blinded women compared with sighted women. In a Swedish cohort study, Feychting et al. found the risk of breast cancer to be lower among blind persons. Pukkala et al. and then Verkasalo et al. observed the decrease of breast cancer risk in women with visual impairments (categorized from moderate low vision to total blindness) in Finland.
Normal breast exhibits rhythmic properties linked to the hormonal environment of the gland in animals and humans, whereas breast cancer in humans is characterized by disruption or modification of normal circadian patterns.
Prolonged light exposure suppresses the night peak release of melatonin—the ‘hormone of the night’ in rodents and in humans. It was shown under highly controlled exposure circumstances, monochromatic light elicited a significant suppression of nocturnal melatonin. Melatonin is a principal hormone of the pineal gland—the small neuroendocrine gland connected with the brain which mediates information on light from the retina of the eyes to the organism.
Recently, the Journal of the National Cancer Institute published two papers reporting a significant increase in the risk of breast cancer among women who frequently did not sleep during the period of the night, around 1:30am, when melatonin levels are typically at their highest. There was increased risk among women sleeping in the brightest bedrooms. Moreover, women who had worked 30 and more years on rotating night shifts had a 36% greater risk of breast cancer compared with workers who had never worked nights.
Several activities of melatonin could be responsible for the indirect inhibition of mammary carcinogenesis. They include the modulation of endocrine (anti-estrogen, anti-gonadotropic effects and inhibition of prolactin level) and immune system, anti-angiogenic, anti-oxidative, anti-proliferative and pro-apoptotic effects in tumors.
Effect of Pineal Peptides on Mammary Carcinogenesis
Most investigators invoked melatonin as a primary mediator of the endocrine functions of the pineal gland. However, some of the effects of the pineal gland obviously might have resulted from pineal peptide secretion. Some crude peptide extracts or purified peptides isolated from pineal glands were shown to have antigonadotropic, metabolic, and antitumor activity.
Epithalamin is a low molecular weight peptide preparation containing a complex of biologically active peptides isolated from cattle pineal glands. In our first experiment, treatment with Epithalamin inhibits significantly (by 80%) the growth of transplantable mammary carcinoma RSM in mice.
Also, Epithalamin was used for treatment of breast cancer patients who had undergone radical mastectomy followed by chemo- or radiotherapy. Later on, these patients were treated only with Epithalamin with intervals between the courses of no more than 6 months during 3–5 years. The patients received Epithalamin in a daily dose of 10 mg for 10 days (100 mg per course). The patients received six to 14 courses of Epithalamin treatment (two to three courses every year). Practically all immune parameters analyzed remained within normal limits or were slightly decreased. Clinical examination confirmed that the patients felt well and worked in their profession. The majority of patients did not manifest relapses or metastases.
Tetrapeptide Epitalon (Ala–Glu–Asp–Gly) has been designed on the basis of Epithalamin amino acid analysis and synthesized at the Laboratory of Peptide Chemistry (headed by Dr EI Grigoriev, PhD) of the St. Petersburg Institute of Bioregulation and Gerontology. Treatment with Epitalon delayed the appearance of mammary tumors and reduced their multiplicity, maximum size and the cumulative number of tumors HER-2/neu transgenic mice. A 3.7-fold reduction in the expression of HER-2/neu mRNA was found in mammary tumors from HER-2/neu transgenic mice treated with Epitalon in comparison with control animals.
The Amazing Conclusion
Data reviewed show the important role of the pineal gland in development of breast cancer. Inhibition of pineal function with the pinealectomy or with exposure to the constant light regimen stimulates mammary carcinogenesis, whereas a light deprivation inhibits the carcinogenesis. Epidemiological observations on increased risk of breast cancer in night shift workers, flight attendants, radio and telegraph operators and on the decreased risk in blind women are in accordance with the results of experiments in rodents. Treatment with pineal indole hormone melatonin inhibits mammary carcinogenesis in pinealectomized rats or animals kept at the LD or the LL regimens.
With regards to the mechanisms involved in the inhibitory effect of peptide Epitalon on mammary carcinogenesis, it was shown that Epitalon increased serum level of melatonin and normalized the circadian rhythm of cortisol in older monkeys. Treatment with Epitalon restored functional activity of neurosecretory cells in the stomach and the thyroid gland. Antioxidative effect of Epitalon was observed in CBA mice. Long-term treatment with Epitalon inhibits age-related increase in the incidence of chromosome aberrations in bone marrow cells of SHR, SAMR-1 and SAMP-1 mice. The down-regulation of HER-2/neu gene expression in mammary adenocarcinoma may be responsible, at least in part, of the anti-tumor effect of the peptide in transgenic mice.
Pineal peptide Epithalamin or tetrapetide Epitalon inhibit mammary tumor development and can be used for prevention of breast cancer in women at risk. Epitalon stimulates the Pineal Gland to produce melatonin, at more normal levels, and normal cycles; which also balances out Cortisol levels and cycles.
Epiatlon's benefits go beyond melatonin and cortisol stimulation, such as increasing telomere length and health, and one of the best investments for GOOD HEALTH and LONGEVITY.
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