Decreased Nocturnal Plasma Melatonin Peak in Patients with Estrogen Receptor Positive Breast Cancer

Tamarkin, Lawrence; Danforth, David N.; Lichter, A P; Demoss, Ernest V.; Cohen, Michael; Chabner, Bruce A.; Lippman, Marc E.

doi:10.1126/science.7079745

Cited by 212 publications

(81 citation statements)

References 9 publications

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“…Women with the lowest peak concentration of melatonin had tumors with the highest concentrations of estrogen receptors. A significant correlation was found between the peak plasma melatonin concentration and the tumor estrogen receptor concentration in 19 of the patients [218] Normal individuals, women with breast cancer, and women at high risk for breast cancer…”

Section: Genomic Stabilitymentioning

confidence: 92%

Melatonin-Induced Oncostasis, Mechanisms and Clinical Relevance

Cardinali¹,

Escames²,

Acuña-Castroviejo³

et al. 2016

J Integr Oncol

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Section: Genomic Stabilitymentioning

confidence: 92%

Melatonin-Induced Oncostasis, Mechanisms and Clinical Relevance

Cardinali¹,

Escames²,

Acuña-Castroviejo³

et al. 2016

J Integr Oncol

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“…These authors suggested that a decrease in pineal function, whatever its cause, and the consequent reduction in melatonin secretion, could induce a state of relative hyperestrogenism, and the early and prolonged exposure of the breast tissue to the estrogens could be involved in the etiology of the breast tumor. A few years later, Tamarkin et al (1982), in an article in Science, described a relationship between plasma melatonin concentration and breast cancer. Women with estrogen receptor (ER)-positive breast adenocarcinomas had nocturnal plasmatic concentrations of melatonin significantly lower than healthy women or women suffering ER-negative breast tumors.…”

Section: The Hypothesis On the Role Of The Pineal Gland And Melatoninmentioning

confidence: 99%

Melatonin and mammary cancer: a short review.

Sánchez‐Barceló¹,

Cos²,

Fernandez³

et al. 2003

Endocrine-Related Cancer

141

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Melatonin is an indolic hormone produced mainly by the pineal gland. The former hypothesis of its possible role in mammary cancer development was based on the evidence that melatonin down-regulates some of the pituitary and gonadal hormones that control mammary gland development and which are also responsible for the growth of hormone-dependent mammary tumors. Furthermore, melatonin could act directly on tumoral cells, as a naturally occurring antiestrogen, thereby influencing their proliferative rate. The first reports revealed a low plasmatic melatonin concentration in women with estrogen receptor (ER)-positive breast tumors. However, later studies on the possible role of melatonin on human breast cancer have been scarce and mostly of an epidemiological type. These studies described a low incidence of breast tumors in blind women as well as an inverse relationship between breast cancer incidence and the degree of visual impairment. Since light inhibits melatonin secretion, the relative increase in the melatonin circulating levels in women with a decreased light input could be interpreted as proof of the protective role of melatonin on mammary carcinogenesis. From in vivo studies on animal models of chemically induced mammary tumorigenesis, the general conclusion is that experimental manipulations activating the pineal gland or the administration of melatonin lengthens the latency and reduces the incidence and growth rate of mammary tumors, while pinealectomy usually has the opposite effects. Melatonin also reduces the incidence of spontaneous mammary tumors in different kinds of transgenic mice (c-neu and N-ras) and mice from strains with a high tumoral incidence.In vitro experiments, carried out with the ER-positive MCF-7 human breast cancer cells, demonstrated that melatonin, at a physiological concentration (1 nM) and in the presence of serum or estradiol: (a) inhibits, in a reversible way, cell proliferation, (b) increases the expression of p53 and p21WAF1 proteins and modulates the length of the cell cycle, and (c) reduces the metastasic capacity of these cells and counteracts the stimulatory effect of estradiol on cell invasiveness; this effect is mediated, at least in part, by a melatonin-induced increase in the expression of the cell surface adhesion proteins E-cadherin and β 1 -integrin.The direct oncostatic effects of melatonin depends on its interaction with the tumor cell estrogen-responsive pathway. In this sense it has been demonstrated that melatonin down-regulates the expression of ERα and inhibits the binding of the estradiol-ER complex to the estrogen response element (ERE) in the DNA. The characteristics of melatonin's oncostatic actions, comprising different aspects of tumor biology as well as the physiological doses at which the effect is accomplished, give special value to these findings and encourage clinical studies on the possible therapeutic value of melatonin on breast cancer.

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“…Raiklin с соавт. выявили повышение уровня МЛТ у больных неза-висимо от локализации опухолевого процесса [32] и, на-против, низкий уровень МЛТ в моче у больных РМЖ [33], а также снижение ночных пиковых концентраций в кро-ви при гормонпозитивном РМЖ [34]. В исследовании Lissoni P. сравнивались концентрации МЛТ у пациентов со злокачественными новообразованиями (n=64) и здоро-вых добровольцев (n=52).…”

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Perspectives of Melatonin Use in Clinical Oncology

Cемиглазова¹,

Osipov²,

Novik³

et al. 2016

Zlokač. opuholi

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Перспективы использования мелатонина в клинической онкологииPerspectives of melatonin use in clinical oncology www.malignanttumours.org • № 4 -2016 г. (20) • MALIGNANT TUMOURSАннотация В 21-м веке достигнуты значительные успехи в лекарственном лечении злокачественных опухолей. Применение новых препаратов позволяет увеличить время до прогрессирования заболевания, продолжительность жизни больных, улучшить ее качество. В последнее время активно изучается противоопухолевая активность гормона эпифиза мелатонина. Этой теме посвящены многочисленные опыты in vitro/ in vivo, в которых показана способность мелатонина тормозить злокачественный рост и потенцировать действие цитостатиков. В данном обзоре освещены данные о использовании мелатонина при лечении пациентов с солидными опухолями. Мелатонин использовался как в монотерапии, так и в комбинации с химиотерапией и иммунотерапией. Согласно результатам этих исследований применение мелатонина приводит к увеличению объективных ответов и общей выживаемости пациентов и к снижению частоты побочных эффектов химиотерапии. Однако этот гормон эпифиза до сих пор рутинно не используется в клинической онкологии и его активность следует изучать в дальнейшем в рамках рандомизированных клинических исследований. AbstractNowadays great successes have been reached in chemotherapy treatment of cancer. New medications let increase time to progression, overall survival and to improve a quality of life. Recently, antitumor activity of melatonin is actively investigated. Many in vitro/in vivo studies are devoted to this topic. In these trials was shown ability of melatonin to inhibit tumor growth and to potentiate the cytotoxic effects of chemotherapy. This review describes the use of melatonin in the treatment of patients with solid tumors. Melatonin has been used in both monotherapy and in combination with chemotherapy and immunotherapy. According to these studies, the use of melatonin increases the objective response and overall survival of patients and reduce the incidence of side effects of chemotherapy. However, this epiphyseal hormone does not routinely used in clinical oncology and will be must to investigate it in more clinical trials. УРОВНИ МЕЛАТОНИНА У БОЛЬНЫХ ЗЛОКАЧЕСТВЕННЫМИ НОВООБРАЗОВАНИЯМИС начала 40-х гг. 20-го века проводились исследования, в ходе которых выявлено, что у онкологических больных наблюдаются морфологические изменения эпифиза. Это проявляется как гипертрофией [26], так и атрофией шиш-ковидной железы [27], появлением множества кист [28,29], кальцификацией эпифиза у пациенток с раком молоч-

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Decreased Nocturnal Plasma Melatonin Peak in Patients with Estrogen Receptor Positive Breast Cancer

Cited by 212 publications

References 9 publications

Melatonin-Induced Oncostasis, Mechanisms and Clinical Relevance

Melatonin-Induced Oncostasis, Mechanisms and Clinical Relevance

Melatonin and mammary cancer: a short review.

Perspectives of Melatonin Use in Clinical Oncology

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