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Melatonin and cancer

Rüdiger Hardeland
Dynamic aspects of melatonin's actions merit increasing future attention. This concerns particularly entirely different effects in senescent, weakened oscillators and in dysregulated oscillators of cancer cells that may be epigenetically blocked. This is especially obvious in the case of sirtuin 1 (SIRT1) which is upregulated by melatonin in aged tissues, but strongly downregulated in several cancer cells. These findings are not at all controversial, but are explained on the basis of divergent changes in weakened and dysregulated oscillators...
October 20, 2016: Journal of Pineal Research
Juan C Mayo, David Hevia, Isabel Quiros-Gonzalez, Aida Rodriguez-Garcia, Pedro Gonzalez-Menendez, Vanesa Cepas, Iván Gonzalez-Pola, Rosa M Sainz
Treatment of prostate cancer (PCa), a leading cause of cancer among males lacks successful strategies especially in advanced, hormone-refractory stages. Some clinical studies have shown an increase in neuroendocrine like cells parallel to the tumor progression but their exact role is a matter of debate. The prostate is a well-known target for melatonin, which reduces PCa cells proliferation and induces neuroendocrine differentiation. To evaluate the mechanisms underlying the indole effects on neuroendocrine differentiation and its impact on PCa progression, we used a cell culture model (LNCaP) and a murine model (TRAMP)...
October 13, 2016: Journal of Pineal Research
Shih-Chi Su, Ming-Ju Hsieh, Wei-En Yang, Wen-Hung Chung, Russel J Reiter, Shun-Fa Yang
Melatonin is a naturally occurring molecule secreted by the pineal gland and known as a gatekeeper of circadian clocks. Mounting evidence indicates that melatonin, employing multiple and interrelated mechanisms, exhibits a variety of oncostatic properties in a myriad of tumors during different stages of their progression. Tumor metastasis, which commonly occurs at the late stage is responsible for the majority of cancer deaths; metastases lead to the development of secondary tumors distant from a primary site...
October 5, 2016: Journal of Pineal Research
Diana I Sánchez, Bárbara González-Fernández, Beatriz San-Miguel, Juan Ortiz de Urbina, Irene Crespo, Javier González-Gallego, María J Tuñón
The sphingosine kinase (SphK)/sphingosine1-phosphate (S1P) pathway is involved in multiple biological processes, including carcinogenesis. Melatonin shows beneficial effects in cell and animal models of hepatocellular carcinoma (HCC), but it is unknown if they are associated with the modulation of the SphK/S1P system, along with different downstream signaling pathways modified in cancer. We investigated effects of melatonin in mice which received diethylnitrosamine (DEN) (35 mg/kg body weight i.p) once a week for 8 weeks...
October 1, 2016: Journal of Pineal Research
Juliana Ramos Lopes, Mayume da Silva Kavagutti, Felipe Arthur Faustino Medeiros, Debora Aparecida Pires De Campos Zuccari
BACKGROUND: The high rates of women's death from breast cancer occur due to acquired resistance by patients to certain treatments, enabling the recurrence and/or tumor growth, invasion and metastasis. It has been demonstrated the presence of cancer stem cells in human tumors, as responsible for recurrence and resistance to therapy. Studies have identified OCT4 as responsible for self-renewal and maintenance of pluripotency of stem cells. Thus, it is interesting to study potential drugs that target this specific population in breast cancer...
September 22, 2016: Anti-cancer Agents in Medicinal Chemistry
Weimin Li, Jiansheng Wu, Zhiyin Li, Zhibo Zhou, Chao Zheng, Le Lin, Binbin Tan, Min Huang, Mengdi Fan
Melatonin is synthesized by the pineal gland and is released into the blood. In the last several years, some studies have shown that melatonin has anticancer properties; however, the mechanisms behind the antitumour traits are unclear, especially in pancreatic cancer. Therefore, in the present study, we investigated the antitumour effects of melatonin on the human pancreatic carcinoma cell line MIA PaCa‑2 and explored its biological mechanisms. MIA PaCa‑2 cells were treated with melatonin, and we used a CCK‑8 assay to evaluate the cell viability...
September 16, 2016: Oncology Reports
Zsofia Kiss, Paramita M Ghosh
The androgen receptor (AR) plays a key role in the development and progression of prostate cancer (CaP). Since the mid-1990s, reports in the literature pointed out higher incidences of CaP in some select groups, such as airline pilots and night shift workers in comparison to those working regular hours. The common finding in these 'high-risk' groups was that they all experienced a deregulation of the body's internal circadian rhythm. Here we discuss how the circadian rhythm affects androgen levels and modulates CaP development and progression...
September 22, 2016: Endocrine-related Cancer
Luiz Gustavo A Chuffa, Luiz Antonio Lupi Júnior, Fábio R F Seiva, Marcelo Martinez, Raquel F Domeniconi, Patricia Fernanda F Pinheiro, Lucilene D Dos Santos, Francisco Eduardo Martinez
To obtain more information into the molecular mechanisms underlying ovarian cancer (OC), we proposed a comparative proteomic analysis in animals receiving long-term melatonin as therapy or only vehicle using multidimensional protein identification combined with mass spectrometry. To induce tumor, a single dose of 100 μg 7,12-dimethylbenz(a)anthracene (DMBA) dissolved in 10 μL of sesame oil was injected under the left ovarian bursa of 20 Fischer 344 rats. The right ovaries were injected with sesame oil only...
October 7, 2016: Journal of Proteome Research
A Pines
Circadian rhythm is an internal biological clock which initiates and monitors various physiological processes with a fixed time-related schedule. The master circadian pacemaker is located in the suprachiasmatic nucleus in the hypothalamus. The circadian clock undergoes significant changes throughout the life span, at both the physiological and molecular levels. This cyclical physiological process, which is very complex and multifactorial, may be associated with metabolic alterations, atherosclerosis, impaired cognition, mood disturbances and even development of cancer...
September 2, 2016: Climacteric: the Journal of the International Menopause Society
David H Lee, Bethany K Asare, Rajendram V Rajnarayanan
Estrogen Receptor Alpha (ER) is expressed in about 70% of breast cancer and mediates various cellular signaling events including cell cycle. The antiestrogen tamoxifen is currently administered to patients in order to induce regression of the tumor growth of estrogen receptor positive (ER+) breast cancer. However, upon continued administration, patients develop resistance to tamoxifen. In addition, calcium binding proteins (EF-hand proteins) such as, Calmodulin and S100, are significantly overexpressed in breast cancer cells, can activate transcription of target genes by directly binding to ER in lieu of estrogen...
October 17, 2016: Cell Cycle
Madhuri S Kurdi, Sindhu Priya Muthukalai
BACKGROUND: The natural hormone melatonin has sleep inducing properties. Insomnia in cancer patients is common. So far, melatonin has been seldom tried for the improvement of sleep in patients with malignancies. Keeping this in mind, we planned and conducted a double-blind study to test the efficacy of melatonin in promoting sleep in patients with malignancies suffering from insomnia. OBJECTIVE: To assess the hypnotic efficacy of oral melatonin in cancer patients with insomnia...
July 2016: Indian Journal of Palliative Care
Seyed Fazel Nabavi, Solomon Habtemariam, Maria Daglia, Antoni Sureda, Eduardo Sobarzo-Sánchez, Zeliha Selamoglu, Mehmet Fuat Gulhan, Seyed Mohammad Nabavi
Melatonin is an indoleamine with potent multifunctional biological and pharmacological effects, both receptor dependent and receptor-independent effects, including antioxidant, anticancer, antitumor, anti-inflammatory, anti-aging, anti-diabetic, antiviral, neuroprotective activities. Melatonin mitigates tissue injury via modification of abnormalities in redox status and other biochemical markers. At the molecular level, the biological and pharmacological activities of melatonin are attributed to the inhibition of nuclear factor-ĸappa beta (NF-ĸB), c-Fos over expression and down-regulation of matrix metalloproteinases-3 (MMP-3), which are regulators of pro-inflammatory and pro-fibrotic cytokines...
August 24, 2016: Current Topics in Medicinal Chemistry
Juliana Lopes, David Arnosti, James E Trosko, Mei-Hui Tai, Debora Zuccari
Cancer stem cells (CSCs) pose a challenge in cancer treatment, as these cells can drive tumor growth and are resistant to chemotherapy. Melatonin exerts its oncostatic effects through the estrogen receptor (ER) pathway in cancer cells, however its action in CSCs is unclear. Here, we evaluated the effect of melatonin on the regulation of the transcription factor OCT4 (Octamer Binding 4) by estrogen receptor alpha (ERα) in breast cancer stem cells (BCSCs). The cells were grown as a cell suspension or as anchorage independent growth, for the mammospheres growth, representing the CSCs population and treated with 10 nM estrogen (E2) or 10 μM of the environmental estrogen Bisphenol A (BPA) and 1 mM of melatonin...
May 2016: Genes & Cancer
Michael D Lovelace, Bianca Varney, Gayathri Sundaram, Nunzio F Franco, Mei Li Ng, Saparna Pai, Chai K Lim, Gilles J Guillemin, Bruce J Brew
The kynurenine pathway (KP) is the major metabolic pathway of the essential amino acid tryptophan (TRP). Stimulation by inflammatory molecules, such as interferon-γ (IFN-γ), is the trigger for induction of the KP, driving a complex cascade of production of both neuroprotective and neurotoxic metabolites, and in turn, regulation of the immune response and responses of brain cells to the KP metabolites. Consequently, substantial evidence has accumulated over the past couple of decades that dysregulation of the KP and the production of neurotoxic metabolites are associated with many neuroinflammatory and neurodegenerative diseases, including Parkinson's disease, AIDS-related dementia, motor neurone disease, schizophrenia, Huntington's disease, and brain cancers...
2016: Frontiers in Immunology
Lulu Mao, Whitney Summers, Shulin Xiang, Lin Yuan, Robert T Dauchy, Amberly Reynolds, Melissa A Wren-Dail, David Pointer, Tripp Frasch, David E Blask, Steven M Hill
: The importance of the circadian/melatonin signal in suppressing the metastatic progression of breast and other cancers has been reported by numerous laboratories including our own. Currently, the mechanisms underlying the anti-metastatic actions of melatonin have not been well established. In the present study, the anti-metastatic actions of melatonin were evaluated and compared on the ERa-negative, Her2-positive SKBR-3 breast tumor cell line and ERa-positive MCF-7 cells overexpressing a constitutively active HER2...
August 17, 2016: Molecular Cancer Research: MCR
Lionel H Opie, Sandrine Lecour
Melatonin, widely used to counter transatlantic travel jet lag and insomnia, is synthesized in the suprachiasmatic nucleus of the anterior pituitary gland. Its release into the circulation is stimulated by the onset of darkness, followed by a progressive decrease in blood levels with the onset of dawn. Melatonin administration can maintain the quality of sleep and help to counteract age-induced cognitive decline. Melatonin can also limit the severity of a variety of cardiovascular and cerebrovascular diseases, diabetes, and cancer...
October 2016: European Heart Journal. Cardiovascular Pharmacotherapy
Shariq Najeeb, Zohaib Khurshid, Sana Zohaib, Muhammad Sohail Zafar
Melatonin (N-acetyl-5-methoxy tryptamine) is a substance secreted by multiple organs in vertebrates. In addition to playing a part in the circadian cycle of the body, melatonin is known to have antioxidant, antiinflammatory, and antioncotic effects on human tissues. Oral cavity is affected by a number of conditions such as periodontitis, mucositis, cancers, and cytotoxicity from various drugs or biomaterials. Research has suggested that melatonin is effective in treating the aforementioned pathologies. Furthermore, melatonin has been observed to enhance osseointegration and bone regeneration...
August 2016: Kaohsiung Journal of Medical Sciences
Shirley Harvey Bush, Nathalie Lacaze-Masmonteil, Marie Theresa McNamara-Kilian, Alistair Richard MacDonald, Sallyanne Tierney, Franco Momoli, Meera Agar, David Christopher Currow, Peter Gerard Lawlor
BACKGROUND: Delirium is a very common and distressing neuropsychiatric syndrome in palliative care. Increasing age, the presence of dementia and advanced cancer are well-known predisposing risk factors for delirium development. Sleep-wake cycle disturbance is frequently seen during delirium and melatonin has a pivotal role in the regulation of circadian rhythms. Current evidence across various settings suggests a potential preventative role for melatonin in patients at risk of delirium, but no studies are currently reported in patients with advanced cancer...
2016: Trials
Russel J Reiter, Juan C Mayo, Dun-Xian Tan, Rosa M Sainz, Moises Alatorre-Jimenez, Lilian Qin
Melatonin is uncommonly effective in reducing oxidative stress under a remarkably large number of circumstances. It achieves this action via a variety of means: direct detoxification of reactive oxygen and reactive nitrogen species and indirectly by stimulating antioxidant enzymes while suppressing the activity of pro-oxidant enzymes. In addition to these well-described actions, melatonin also reportedly chelates transition metals, which are involved in the Fenton/Haber-Weiss reactions; in doing so, melatonin reduces the formation of the devastatingly toxic hydroxyl radical resulting in the reduction of oxidative stress...
October 2016: Journal of Pineal Research
Noble Kumar Talari, Manas Panigrahi, Sailaja Madigubba, Sundaram Challa, Prakash Babu Phanithi
Meningiomas are the neoplasms that arise from the arachnoid cells of the meninges. It was reported that cancer cells escape from immune system through the metabolism of an aromatic essential amino acid tryptophan (TRP) via Kynurenine (KYN) pathway. However, the role of TRP metabolites such as, 5-Hydroxy tryptophan (5-HTP), 5-Hydroxy tryptamine (5-HT), N-acetyl serotonin (NAS), Melatonin (MEL), KYN, N-acetyl tryptamine, 5-Hydroxy indole acetic acid (5-HIAA) and 5-Methoxy indole acetic acid is not yet evaluated in human meningioma...
July 29, 2016: Journal of Neuro-oncology
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