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Old 12-02-2007, 05:56 AM   #1
R.B.
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Melatonin cancer treatment biology etc

http://www.pubmedcentral.nih.gov/art...?artid=1317110

An interesting trial on melatonin.

It mentions BC and synergies with some cancer treatments as well as describing the wider role of melatonin.

RB
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Old 12-03-2007, 05:17 PM   #2
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http://jco.ascopubs.org/cgi/content/abstract/3/7/941

I have only seen the abstract of this. Something I found whilst looking for something else. Thought provoking.

http://jco.ascopubs.org/cgi/content/abstract/3/7/941

Journal of Clinical Oncology, Vol 3, 941-948, Copyright © 1985 by American Society of Clinical Oncology

ARTICLES
Plasma melatonin and the hormone-dependency of human breast cancer

DN Danforth Jr, L Tamarkin, JJ Mulvihill, CS Bagley and ME Lippman

"Further, a strong inverse correlation was observed between the plasma melatonin concentration and the quantities of ER and PR in the primary tumor: the lower the plasma melatonin concentration the greater the amount of either receptor in the primary tumor."

"These findings suggest an important relationship between the plasma melatonin diurnal rhythm and the hormone dependency of human breast cancer, and may have implications for both the prognosis and treatment of this malignancy."
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Old 12-02-2008, 11:38 AM   #3
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Integr Cancer Ther. 2008 Sep;7(3):189-203. Links
Therapeutic actions of melatonin in cancer: possible mechanisms.

Srinivasan V, Spence DW, Pandi-Perumal SR, Trakht I, Cardinali DP.
Department of Physiology, School of Medical Sciences, University Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.
Melatonin is a phylogenetically well-preserved molecule with diverse physiological functions. In addition to its well-known regulatory control of the sleep/wake cycle, as well as circadian rhythms generally, melatonin is involved in immunomodulation, hematopoiesis, and antioxidative processes. Recent human and animal studies have now shown that melatonin also has important oncostatic properties. Both at physiological and pharmacological doses melatonin exerts growth inhibitory effects on breast cancer cell lines. In hepatomas, through its activation of MT1 and MT2 receptors, melatonin inhibits linoleic acid uptake, thereby preventing the formation of the mitogenic metabolite 1,3-hydroxyoctadecadienoic acid. In animal model studies, melatonin has been shown to have preventative action against nitrosodiethylamine (NDEA)-induced liver cancer. Melatonin also inhibits the growth of prostate tumors via activation of MT1 receptors thereby inducing translocation of the androgen receptor to the cytoplasm and inhibition of the effect of endogenous androgens. There is abundant evidence indicating that melatonin is involved in preventing tumor initiation, promotion, and progression. The anticarcinogenic effect of melatonin on neoplastic cells relies on its antioxidant, immunostimulating, and apoptotic properties. Melatonin's oncostatic actions include the direct augmentation of natural killer (NK) cell activity, which increases immunosurveillance, as well as the stimulation of cytokine production, for example, of interleukin (IL)-2, IL-6, IL-12, and interferon (IFN)-gamma. In addition to its direct oncostatic action, melatonin protects hematopoietic precursors from the toxic effect of anticancer chemotherapeutic drugs. Melatonin secretion is impaired in patients suffering from breast cancer, endometrial cancer, or colorectal cancer. The increased incidence of breast cancer and colorectal cancer seen in nurses and other night shift workers suggests a possible link between diminished secretion of melatonin and increased exposure to light during nighttime. The physiological surge of melatonin at night is thus considered a "natural restraint" on tumor initiation, promotion, and progression.
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Old 12-02-2008, 04:47 PM   #4
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Thanks for posting that Rich

Interesting trial summary
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Old 04-11-2009, 10:22 AM   #5
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1: Expert Rev Mol Med. 2009 Feb 5;11:e5. Links
Melatonin and breast cancer: cellular mechanisms, clinical studies and future perspectives.

Grant SG, Melan MA, Latimer JJ, Witt-Enderby PA.
University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15232, USA.
Recent studies have suggested that the pineal hormone melatonin may protect against breast cancer, and the mechanisms underlying its actions are becoming clearer. Melatonin works through receptors and distinct second messenger pathways to reduce cellular proliferation and to induce cellular differentiation. In addition, independently of receptors melatonin can modulate oestrogen-dependent pathways and reduce free-radical formation, thus preventing mutation and cellular toxicity. The fact that melatonin works through a myriad of signalling cascades that are protective to cells makes this hormone a good candidate for use in the clinic for the prevention and/or treatment of cancer. This review summarises cellular mechanisms governing the action of melatonin and then considers the potential use of melatonin in breast cancer prevention and treatment, with an emphasis on improving clinical outcomes
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Old 04-11-2009, 10:33 AM   #6
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Histol Histopathol. 2009 Jun;24(6):789-99. Links
Melatonin modulates microfilament phenotypes in epithelial cells: implications for adhesion and inhibition of cancer cell migration.

BenĂ*tez-King G, Soto-Vega E, RamĂ*rez-Rodriguez G.
Neuropharmacology Department, Division of Clinical Investigations, National Institute of Psychiatry Ramón de la Fuente Muñiz, Mexico, DF. Mexico. bekin@imp.edu.mx
Cell migration and adhesion are cytoskeleton- dependent functions that play a key role in epithelial physiology. Specialized epithelial cells in water transport have specific microfilament rearrangements that make these cells adopt a polyhedral shape, forming a sealed monolayer which functions as permeability barrier. Also, specific polarized microfilament phenotypes are formed at the front and the rear of migratory epithelial cells. In pathological processes such as cancer, increased migration occurs in invasive cells driven by the formation of polarized and differential microfilament phenotypes. Melatonin, the main product secreted by the pineal gland during dark phase of the photoperiod, acts as a cytoskeletal modulator in normal and cancer cells. In this paper we will summarize evidence supporting that melatonin acts as a microfilament modulator in epithelial MDCK cells, and we will describe its effects on cytoskeleton organization involved in the mechanism by which melatonin synchronizes water transport. In addition, we will review recent data that indicate that melatonin is able to switch microfilament phenotypes in MCF-7 human mammary cancer cells, from invasive migratory cells to dormant microfilament phenotypes that occur in non- migratory cells. Moreover, we will discuss the implications of the cytoskeleton as therapeutic target for cancer cells.
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Old 04-11-2009, 10:36 AM   #7
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1: J Pineal Res. 2009 Mar;46(2):172-80. Epub 2008 Oct 29. Links
Evidence for a biphasic apoptotic pathway induced by melatonin in MCF-7 breast cancer cells.

Cucina A, Proietti S, D'Anselmi F, Coluccia P, Dinicola S, Frati L, Bizzarri M.
Surgery Department "Pietro Valdoni", Rome, Italy.
Previous investigations demonstrated that melatonin exerts an oncostatic action on estrogen-responsive breast cancer, both in vitro and in vivo. Nevertheless, the pro-apoptotic effect of melatonin is still a matter of debate. An experimental study was undertaken to focus on melatonin-related apoptosis and to identify the apoptotic pathways involved. Whole cell-count, flow-cytometry analysis and proteins involved in apoptotic pathways [p53, p73, murine double minute 2 (MDM2), caspases-9,-7,-6, cleaved-poly ADP ribose polymerase (PARP), Bcl-2, Bax and apoptotic inducing factor (AIF)] were investigated in human MCF-7 breast cancer cells treated with physiological (1 nM) concentration of melatonin. Melatonin exerts a significant growth-inhibitory effect on MCF-7 cells, becoming evident after 72 hr and thereafter increasing linearly up to 144 hr. In this model, the growth-inhibition is transforming growth factor beta 1 (TGFbeta1)-dependent and it might be reversed by adding an anti-TGFbeta1 antibody. Melatonin induces a significant rise in apoptotic rate, at both 24 and 96 hr. The anti-TGFbeta1 antibody almost completely suppresses melatonin-related late apoptosis; however, early apoptosis is unaffected. Early programmed cell death is associated with a significant increase in the p53/MDM2 ratio and in AIF release, without modifications in caspase activity or cleaved-PARP levels. Activated caspases-9 and -7 and cleaved-PARP increased significantly at 96 hr, concomitantly with a down-regulation of the Bcl-2/Bax ratio. These data suggest that two distinct apoptotic processes are triggered by melatonin in MCF-7 cells: an early, TGFbeta1 and caspase-independent response, and a late apoptotic TGFbeta1-dependent process in which activated-caspase-7 is likely to be the terminal effector.
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Old 04-11-2009, 11:09 AM   #8
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1: Neuro Endocrinol Lett. 2008 Dec;29(6):815-21.Links
A generalized theory of carcinogenesis due to chronodisruption.

Erren TC, Reiter RJ.
Institute and Policlinic for Occupational and Social Medicine, School of Medicine and Dentistry, University of Cologne, Cologne, Germany. tim.erren@uni-koeln.de
For two decades, research has been suggested and conducted into the causation and development of cancers in seemingly diverse and unrelated populations such as blind individuals, shift-workers, flight personnel, Arctic residents and subsets of sleepers. One common denominator of these investigations is "melatonin". Another common denominator is that all these studies implicitly pursued the validity of the so-called "melatonin hypothesis", of a corollary and of associated predictions which can be united in our proposed theory of "carcinogenesis due to chronodisruption". The new theory suggests that the various predictions investigated between 1987 and 2008 represent different aspects of the same problem. Indeed, abundant experimental evidence supports the notion that the final common cause of many cases of cancer may be what has been termed chronodisruption (CD), a relevant disturbance of the temporal organization or order of physiology, endocrinology, metabolism and behaviour. While melatonin as a key time messenger and time keeper can be a marker of CD, it is probably only partially related to the differential cancer occurrence apparent in individuals who chronically or frequently experience an excess or deficit of chronodisruption.
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Old 04-11-2009, 11:12 AM   #9
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1: Curr Cancer Drug Targets. 2008 Dec;8(8):691-702. Links
Melatonin as a selective estrogen enzyme modulator.

Cos S, González A, MartĂ*nez-Campa C, Mediavilla MD, Alonso-González C, Sánchez-BarcelĂł EJ.
Department of Physiology and Pharmacology, School of Medicine, University of Cantabria, Santander, Spain. coss@unican.es
Melatonin exerts oncostatic effects on different kinds of tumors, especially on hormone-dependent breast cancer. The general conclusion is that melatonin, in vivo, reduces the incidence and growth of chemically-induced mammary tumors in rodents, and, in vitro, inhibits the proliferation and invasiveness of human breast cancer cells. Both studies support the hypothesis that melatonin inhibits the growth of breast cancer by interacting with estrogen-signaling pathways through three different mechanisms: (a) the indirect neuroendocrine mechanism which includes the melatonin down-regulation of the hypothalamic-pituitary-reproductive axis and the consequent reduction of circulating levels of gonadal estrogens, (b) direct melatonin actions at tumor cell level by interacting with the activation of the estrogen receptor, thus behaving as a selective estrogen receptor modulator (SERM), and (c) the regulation of the enzymes involved in the biosynthesis of estrogens in peripheral tissues, thus behaving as a selective estrogen enzyme modulator (SEEM). As melatonin reduces the activity and expression of aromatase, sulfatase and 17beta-hydroxysteroid dehydrogenase and increases the activity and expression of estrogen sulfotransferase, it may protect mammary tissue from excessive estrogenic effects. Thus, a single molecule has both SERM and SEEM properties, one of the main objectives desired for the breast antitumoral drugs. Since the inhibition of enzymes involved in the biosynthesis of estrogens is currently one of the first therapeutic strategies used against the growth of breast cancer, melatonin modulation of different enzymes involved in the synthesis of steroid hormones makes, collectively, this indolamine an interesting anticancer drug in the prevention and treatment of estrogen-dependent mammary tumors.
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Old 04-15-2009, 10:39 AM   #10
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from RB on another thread:

Melatonin uptake and growth prevention in rat hepatoma 7288CTC in response to dietary melatonin: melatonin receptor-mediated inhibition of tumor linoleic acid metabolism to the growth signaling molecule 13-hydroxyoctadecadienoic acid and the potential role of phytomelatonin*

David E. Blask1, Robert T. Dauchy, Leonard A. Sauer and Jean A. Krause

Laboratory of Chrono-Neuroendocrine Oncology, Bassett Research Institute, One Atwell Road, Cooperstown, NY 13326, USA

Both physiological and pharmacological levels of the pineal hormone melatonin exhibit substantial anticancer activity in tissue-isolated rat hepatoma 7288CTC via melatonin receptor-mediated blockade of tumor uptake of linoleic acid (LA) and its metabolism to the mitogenic signaling molecule 13-hydroxyoctadecadienoic acid (13-HODE). Melatonin is also present in significant amounts in edible plants and is supplied in nutritional supplements. We confirmed the presence of significant quantities of melatonin in 20 varieties of edible plants. In pinealectomized tumor-free rats, 3 weeks of ingestion of either 5 or 50 µg/day of melatonin contained in a semi-purified diet resulted in a dose-dependent elevation in steady-state plasma melatonin levels within the nocturnal physiological range. In pineal-intact tumor-bearing rats, the daily intake of 5 µg/day of melatonin for 3 weeks resulted in an enhanced amplitude and duration of the nocturnal melatonin levels within physiological circulating limits. The nocturnal melatonin amplitude in rats ingesting 500 ng of melatonin/day remained within the physiological range. A dose-related increase in tumor concentrations of melatonin occurred in animals ingesting melatonin from the diet. Perfusion of tumors in situ with physiological, nocturnal blood levels of melatonin resulted in a mean 31% uptake and retention of the melatonin. Chronic ingestion of 50 ng, 500 ng or 5 µg of melatonin/day supplied in a semi-purified 5% corn oil diet led to a significant dose-dependent reduction in the rates of tumor total fatty acid uptake, LA uptake, 13-HODE production and tumor growth. The co-ingestion of melatonin receptor antagonist S20928 completely blocked the effects and prevented the intra-tumoral accumulation of melatonin. Melatonin receptor-mediated suppression of tumor growth, LA uptake and metabolism, and stimulation of tumor melatonin uptake and retention in response to the dietary intake of phytomelatonin from edible plants or melatonin from nutritional supplements, could play an important role in cancer growth prevention.



Effect of Melatonin and Linolenic Acid on Mammary Cancer in Transgenic Mice with c-neu Breast Cancer Oncogene

Ghanta N. Rao, Elizabeth Ney and Ronald A. Herbert

Abstract Breast cancer is one of the most common cancers and is a leading cause of mortality in women. The TG.NK transgenic mouse line expresses the c-neu breast cancer oncogene under the control of a MMTV promoter and appears to be a useful animal model for evaluation of intervention strategies to delay/prevent breast cancer. Fiber-rich nonpurified diet (NTP-2000) and some retinoid analogues have been shown to significantly delay the development of mammary cancer in the TG.NK model. Four-week-old hemizygous TG.NK female mice with MMTV/c-neu oncogene fed NTP-2000 diet were gavaged with 0.05–0.2thinspml of flaxseed oil as the source of ohgr-3 rich PUFA, or melatonin at 50–200thinspmg/kg or a combination of 0.10thinspml flaxseed oil and 50thinspmg/kg melatonin in a gavage volume of 0.2thinspml per mouse with corn oil as the vehicle for 30 weeks. The time course of the mammary tumor incidence pattern was advanced by flaxseed oil compared to the control. At the high dose (0.2thinspml) of flaxseed oil, when the ohgr-6: ohgr-3 PUFA ratio was closer to 1, there was some delay in the growth of mammary tumors. Melatonin delayed the appearance of palpable tumors and the growth of the tumors with a dose-related statistically significant negative trend for the incidence of tumors. The combination of flaxseed oil and melatonin caused a significant decrease in the number of tumors and tumor weight per mouse compared to the control and to flaxseed oil but not to melatonin alone. Flaxseed oil may delay the growth of mammary tumors if the ohgr-6hgr-3 PUFA ratio of fat consumed is closer to 1. Melatonin has the potential to markedly delay the appearance of palpable mammary tumors. Studies are in progress with the TG.NK mouse model to understand the histological and molecular changes associated with the dose-response pattern of mammary tumor incidence and growth after treatment with a broad range of doses of melatonin.



New Actions of Melatonin on Tumor Metabolism and Growth
DavidE. Blask, LeonardA. Sauer, RobertT. Dauchy, EugeneW. Holowachuk, MaryS. Ruhoff

Bassett Research Institute, Mary Imogene Bassett Hospital, Cooperstown, N.Y., USA

Melatonin is an important inhibitor of cancer growth promotion while the essential polyunsaturated fatty acid, linoleic acid is an important promoter of cancer progression. Following its rapid uptake by tumor tissue, linoleic acid is oxidized via a lipoxygenase to the growth-signaling molecule, 13-hydroxyoctadecadienoic acid (13-HODE) which stimulates epidermal growth factor (EGF)-dependent mitogenesis. The uptake of plasma linoleic acid and its metabolism to 13-HODE by rat hepatoma 7288CTC, which expresses both fatty acid transport protein and melatonin receptors, is inhibited by melatonin in a circadian-dependent manner. This inhibitory effect of melatonin is reversible with either pertussis toxin, forskolin or cAMP. While melatonin inhibits tumor linoleic acid uptake, metabolism and growth, pinealectomy or constant light exposure stimulates these processes. Thus, melatonin and linoleic acid represent two important environmental signals that interact in a unique manner to regulate tumor progression and ultimately the host-cancer balance.
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Old 09-23-2009, 09:08 PM   #11
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Re: Melatonin cancer treatment biology etc

info against melatonin? I've been wondering about the negatives of melatonin's antioxidant qualities in established cancer:

1: Ann N Y Acad Sci. 2009 Aug;1171:472-8. Links
Intracellular prooxidant activity of melatonin induces a survival pathway involving NF-kappaB activation.

Cristofanon S, Uguccioni F, Cerella C, Radogna F, Dicato M, Ghibelli L, Diederich M.
Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Fondation Recherche sur le Cancer et les Maladies du Sang, Hôpital Kirchberg, Luxembourg. silvia.cristofanon@lbmcc.lu
We have shown that melatonin exerts a prooxidant activity in U937 cells, a tumor human promonocytic cell line. (1) Here we show that melatonin induces a strong canonical activation of NF-kappaB, inducing IkappaBalpha degradation and the consequential nuclear translocation of p50/p65 subunits. The timing of NF-kappaB activation overlaps with the timing of reactive oxygen species (ROS) production due to melatonin. Overexpression of dominant-negative IkappaB, which prevents a possible NF-kappaB activation, transformed melatonin in a proapoptotic molecule. These data indicate for the first time that melatonin can trigger NF-kappaB activation and might suggest a possible role for ROS induced by melatonin. Results indicate a possible involvement in the survival pathway of melatonin-generated ROS as secondary messengers.
PMID: 19723091 [PubMed - indexed for MEDLINE]
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Old 10-31-2009, 01:49 PM   #12
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Re: Melatonin cancer treatment biology etc

Molecular Diagnostics

British Journal of Cancer (2009) 101, 1613–1619. doi:10.1038/sj.bjc.6605336 www.bjcancer.com
Published online 22 September 2009
Melatonin inhibits aromatase promoter expression by regulating cyclooxygenases expression and activity in breast cancer cells

C MartĂ*nez-Campa1, A González1, M D Mediavilla1, C Alonso-González1, V Alvarez-GarcĂ*a1, E J Sánchez-BarcelĂł1 and S Cos1
1Department of Physiology and Pharmacology, School of Medicine, University of Cantabria, 39011 Santander, Spain
Correspondence: Dr S Cos, Departamento de FisiologĂ*a y FarmacologĂ*a, Facultad de Medicina, Universidad de Cantabria, Cardenal Herrera Oria s/n, 39011 Santander, Spain. E-mail: coss@unican.es
Received 29 May 2009; Revised 19 August 2009; Accepted 1 September 2009; Published online 22 September 2009.

Top of pageAbstract

Background:

Melatonin reduces the development of breast cancer interfering with oestrogen-signalling pathways, and also inhibits aromatase activity and expression. Our objective was to study the promoters through which melatonin modifies aromatase expression, evaluate the ability of melatonin to regulate cyclooxygenases and assess whether the effects of melatonin are related to its effects on intracellular cAMP, in MCF-7 cells.

Methods:

Total aromatase mRNA, aromatase mRNA promoter regions and cyclooxygenases mRNA expression were determined by real-time RT–PCR. PGE2 and cAMP were measured by kits.

Results:

Melatonin downregulated the gene expression of the two major specific aromatase promoter regions, pII and pI.3, and also that of the aromatase promoter region pI.4. Melatonin 1 nM was able to counteract the stimulatory effect of tetradecanoyl phorbol acetate on PGE2 production and inhibit COX-2 and COX-1 mRNA expression. Melatonin 1 nM elicited a parallel time-dependent decrease in both cyclic AMP formation and aromatase mRNA expression.

Conclusions:

This study shows that melatonin inhibits aromatase activity and expression by regulating the gene expression of specific aromatase promoter regions. A possible mechanism for these effects would be the regulation by melatonin of intracellular cAMP levels, mediated by an inhibition of cyclooxygenase activity and expression.

Keywords:

melatonin, pineal, MCF-7 cells, breast cancer, aromatase
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Old 10-31-2009, 02:17 PM   #13
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Re: Melatonin cancer treatment biology etc

Cancer Lett. 2009 Jul 24. [Epub ahead of print]
Melatonin sensitizes human malignant glioma cells against TRAIL-induced cell death.

MartĂ*n V, GarcĂ*a-Santos G, Rodriguez-Blanco J, Casado-Zapico S, Sanchez-Sanchez A, AntolĂ*n I, Medina M, Rodriguez C.
Departamento de MorfologĂ*a y BiologĂ*a Celular, Spain; Instituto Universitario de OncologĂ*a del Principado de Asturias (IUOPA), Spain.
Despite the common expression of death receptors, many types of cancer including gliomas are resistant to the death receptor ligand (TRAIL). Melatonin antitumoral actions have been extensively described, including oncostatic properties on several tumor types and improvement of chemotherapeutic regimens. Here, we found that melatonin effectively increase cell sensitivity to TRAIL-induced cell apoptosis in A172 and U87 human glioma cells. The effect seems to be related to a modulation of PKC activity which in turns decreases Akt activation leading to an increase in death receptor 5 (DR5) levels and a decrease in the antiapoptotic proteins survivin and bcl-2 levels.

PMID: 19632770 [PubMed - as supplied by publisher]


Postepy Hig Med Dosw (Online). 2009 Sep 15;63:425-34.
[MT1 melatonin receptors and their role in the oncostatic action of melatonin]

[Article in Polish]
Danielczyk K, Dziegiel P.
Katedra i Zakład Histologii i Embriologii Akademii Medycznej im. PiastĂłw Slaskich we Wrocławiu.
Melatonin, the main hormone produced by the pineal gland, strongly inhibits the growth of cancer cells in vitro and in vivo. Some publications indicate that the addition of melatonin to culture medium slows the proliferation of some cancer cell lines. It is also suggested that melatonin used as an adjuvant benefits the effectiveness and tolerance of chemotherapy. The mechanisms of this are not fully understood, but melatonin receptors might be one of the most important elements. Two distinct types of membrane-bound melatonin receptors have been identified in humans: MT1 (Mel1a) and MT2 (Mel1b) receptors. These subtypes are 60% homologous at the amino-acid level. MT1 receptors are G-protein-coupled receptors. Through the a subunit of G protein, melatonin receptors stimulate an adenylate cyclase and decrease the level of cAMP. This has a significant influence on cell proliferation and has been confirmed in many tests on different cell lines, such as S-19, B-16 murine melanoma cells, and breast cancer cells. It seems that expression of the MT1 melatonin receptors benefits the efficacy of melatonin treatment. Melatonin and its receptors may provide a promising way to establish new alternative therapeutic approaches in human cancer prevention.

PMID: 19837985 [PubMed - in process]





Biochim Biophys Acta. 2006 May-Jun;1757(5-6):573-89. Epub 2006 Apr 17.
Melatonin as antioxidant, geroprotector and anticarcinogen.

Anisimov VN, Popovich IG, Zabezhinski MA, Anisimov SV, Vesnushkin GM, Vinogradova IA.
Department of Carcinogenesis and Oncogerontology, N.N. Petrov Research Institute of Oncology, Pesochny-2, St. Petersburg 197758, Russia. aging@mail.ru
The effect of the pineal indole hormone melatonin on the life span of mice, rats and fruit flies has been studied using various approaches. It has been observed that in female CBA, SHR, SAM and transgenic HER-2/neu mice long-term administration of melatonin was followed by an increase in the mean life span. In rats, melatonin treatment increased survival of male and female rats. In D. melanogaster, supplementation of melatonin to nutrient medium during developmental stages produced contradictory results, but and increase in the longevity of fruit flies has been observed when melatonin was added to food throughout the life span. In mice and rats, melatonin is a potent antioxidant both in vitro and in vivo. Melatonin alone turned out neither toxic nor mutagenic in the Ames test and revealed clastogenic activity at high concentration in the COMET assay. Melatonin has inhibited mutagenesis and clastogenic effect of a number of indirect chemical mutagens. Melatonin inhibits the development of spontaneous and 7-12-dimethlbenz(a)anthracene (DMBA)- or N-nitrosomethylurea-induced mammary carcinogenesis in rodents; colon carcinogenesis induced by 1,2-dimethylhydrazine in rats, N-diethylnitrosamine-induced hepatocarcinogenesis in rats, DMBA-induced carcinogenesis of the uterine cervix and vagina in mice; benzo(a)pyrene-induced soft tissue carcinogenesis and lung carcinogenesis induced by urethan in mice. To identify molecular events regulated by melatonin, gene expression profiles were studied in the heart and brain of melatonin-treated CBA mice using cDNA gene expression arrays (15,247 and 16,897 cDNA clone sets, respectively). It was shown that genes controlling the cell cycle, cell/organism defense, protein expression and transport are the primary effectors for melatonin. Melatonin also increased the expression of some mitochondrial genes (16S, cytochrome c oxidases 1 and 3 (COX1 and COX3), and NADH dehydrogenases 1 and 4 (ND1 and ND4)), which agrees with its ability to inhibit free radical processes. Of great interest is the effect of melatonin upon the expression of a large number of genes related to calcium exchange, such as Cul5, Dcamkl1 and Kcnn4; a significant effect of melatonin on the expression of some oncogenesis-related genes was also detected. Thus, we believe that melatonin may be used for the prevention of premature aging and carcinogenesis.

PMID: 16678784 [PubMed - indexed for MEDLINE]
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Old 10-31-2009, 09:57 PM   #14
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Re: Melatonin cancer treatment biology etc

I have a theory on my cancer. I developed characteristics of autism when I was in kindergarten.

Autistism shares similar characteristics to mercury poisoning. They say autistics are low in melatonin.

Perhaps this is the beginning of the cancer disease chain. The common link in "advanced" countries being the increased vaccination rates with thimerosol as a preservative.

Autistics are more likely to have allergies, asthma, selective IgA deficiency (sIgAd), enhanced expression of HLA-DR antigen, and an absence of interleukin-2 receptors, as well as familial autoimmunity and a variety of autoimmune phenomena. These include elevated serum IgG and ANA titers, IgM and IgG brain antibodies, and myelin basic protein (MBP) antibodies (103-110). Similarly, atypical responses to Hg have been ascribed to allergic or autoimmune reactions (8), and genetic predisposition to such reactions may explain why Hg sensitivity varies so widely by individual (88,111). Children who developed acrodynia were more likely to have asthma and other allergies (11); IgG brain autoantibodies, MBP, and ANA have been found in HgP subjects (18,111,112); and mice genetically prone to develop autoimmune diseases "are highly susceptible to mercury-induced immunopathological alterations" even at the lowest doses (113). Additionally, many autistics have reduced natural killer cell (NK) function, as well as immune-cell subsets shifted in a Th2 direction and increased urine neopterin levels, indicating immune system activiation (103,114-116). Depending upon genetic predisposition, Hg can induce immune activation, an expansion of Th2 subsets, and decreased NK activity (117-120).

http://www.autism.com/triggers/vaccine/mercury.htm
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Traditional Treatment: Mastectomy and Axillary Node Dissection followed by Taxotere, 6 treatments and 1 year of Herceptin, no radiation
Former Chemo Ninja "Takizi Zukuchiri"

Additional treatments:
GP2 vaccine, San Antonio Med Ctr
Prescriptive Exercise for Cancer Patients
ENERGY Study, UCSD La Jolla

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The content of my posts are meant for informational purposes only. The medical information is intended for general information only and should not be used in any way to diagnose, treat, cure, or prevent disease
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