Abstract：
:Glioblastoma stem-like cells (GSCs) displaying self-renewing and tumor-propagating capacity play a particularly important role in maintaining tumor growth, therapeutic resistance, and tumor recurrence. Therefore, new therapeutic strategies focusing on impairing GSC maintenance are urgently needed. Here, we used GSCs isolated from surgical specimens from patients with glioblastoma multiforme (GBM) to study the roles and underlying mechanisms associated with melatonin in GSC biology. The results showed that melatonin directly targeted glioma tumor cells by altering GSC biology and inhibiting GSC proliferation. Additionally, melatonin altered profile of transcription factors to inhibit tumor initiation and propagation. Furthermore, EZH2 S21 phosphorylation and EZH2-STAT3 interaction in GSCs were impaired following melatonin treatment. These results suggested that melatonin attenuated multiple key signals involved in GSC self-renewal and survival, and further supported melatonin as a promising GBM therapeutic.
journal_name
J Pineal Resjournal_title
Journal of pineal researchauthors
Chen X,Hao A,Li X,Du Z,Li H,Wang H,Yang H,Fang Zdoi
10.1111/jpi.12341subject
Has Abstractpub_date
2016-09-01 00:00:00pages
208-17issue
2eissn
0742-3098issn
1600-079Xjournal_volume
61pub_type
杂志文章abstract：:The serum levels of the pineal hormone melatonin were determined by radioimmunoassay (RIA) in 4-h intervals throughout a 24-h period in elderly men with different types of prostate tumors: benign prostatic hyperplasia (BPH, n = 13), incidental carcinoma (PCi, n = 5), and nonmetastasizing carcinoma (PC, n = 9), as well...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1985.tb00633.x
更新日期：1985-01-01 00:00:00
abstract：:Melatonin is known to regulate a variety of physiological processes including control of circadian rhythms, regulation of seasonal reproductive function, regulation of body temperature, and so forth. Accumulating evidence from in vitro and in vivo experiments using rodent and chicken has also suggested that melatonin ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2006.00410.x
更新日期：2007-04-01 00:00:00
abstract：:Djungarian hamsters kept in long photoperiod (16:8 L:D) were injected daily at 0800, 1200, or 1600 with 25 micrograms of melatonin. During 90 days of treatment, body weight and fur coloration were checked at weekly intervals, and at the end of the treatment the reproductive status of the hamsters and their thermoregul...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1985.tb00719.x
更新日期：1985-01-01 00:00:00
abstract：:A review of the literature indicates that the absolute oral bioavailability of exogenous melatonin in humans or in preclinical animal models has not been adequately characterized; hence, this study was undertaken. Pharmacokinetics of melatonin was studied in rats, dogs, and monkeys following intravenous and oral admin...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1997.tb00302.x
更新日期：1997-01-01 00:00:00
abstract：:Maternal hyperthermia induces early embryonic death via increased oxidative stress to the embryo. In this study, we examined whether melatonin administered to heat-stressed pregnant mice would reduce hyperthermia-induced embryonic death. Mice were heat stressed (12 hr at 35 degrees C, 60% relative humidity) on the day...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2005.00260.x
更新日期：2005-10-01 00:00:00
abstract：:Melatonin plays an important role in regulating circadian rhythms. It also acts as a potent antioxidant and regulates glucose and lipid metabolism, although the exact action mechanism is not clear. The α2-HS-glycoprotein gene (AHSG) and its protein, fetuin-A (FETUA), are one of the hepatokines and are known to be asso...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12493
更新日期：2018-09-01 00:00:00
abstract：:Melatonin is part of the evolutionary conserved highly functional network in vertebrates. It plays a central role in the adaptative behavior of the animal to the environment, including entrainment of daily and annual physiological rhythms, reproductive behavior, food intake, locomotor activity, growth, and breeding pe...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12149
更新日期：2014-08-01 00:00:00
abstract：:Recently, a species-dependent distribution of melatonin binding sites have been found in lamina I-V and lamina X of the spinal cord. In order to learn more about the function of spinal melatonin receptors, we investigated (i) the gene expression for melatonin receptor subtypes in lumbar and thoracal spinal cord tissue...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1034/j.1600-079x.2003.00047.x
更新日期：2003-08-01 00:00:00
abstract：:Lower global cognitive function scores are a common symptom of autism spectrum disorders (ASDs). This study investigates the effects of melatonin on hippocampal serine/threonine kinase signaling in an experimental ASD model. We found that chronic melatonin (1.0 or 5.0 mg/kg/day, 28 days) treatment significantly rescue...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12081
更新日期：2014-01-01 00:00:00
abstract：:There are functional inter-relationships between the beta cells of the endocrine pancreas and the pineal gland, where the synchronizing circadian molecule melatonin originates. The aim of this study was to elucidate a putative interaction between insulin and melatonin in diabetic patients and a diabetic rat model. We ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2005.00287.x
更新日期：2006-03-01 00:00:00
abstract：:Rat pineal hydroxyindole-O-methyltransferase (HIOMT; EC 2.1.1.4) was purified by affinity chromatography using an S-adenosyl-L-homocysteine agarose column. This single-step procedure, which is rapid, simple, and applicable to small quantities of tissue, gave a large enrichment of a protein (Mr approximately 38,000) id...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1986.tb00761.x
更新日期：1986-01-01 00:00:00
abstract：:This study examined plasma melatonin levels and the suppressant effect of light on melatonin production in the squirrel monkey. Monkeys were maintained on a 12:12 light-dark cycle (LD 12:12) with lights on from 07:00 to 19:00. Plasma levels of melatonin were determined by gas chromatography negative chemical ionizatio...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1990.tb00689.x
更新日期：1990-01-01 00:00:00
abstract：:The cellular proliferative activity in the adult rat pineal gland was studied using bromodeoxyuridine immunohistochemistry during the light and dark phases of an artificial 12L:12D photoperiod. The results showed statistically significant differences in the number of labeled cells between the light and dark phases, wi...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1997.tb00327.x
更新日期：1997-08-01 00:00:00
abstract：:N-acetylserotonin methyltransferase (ASMT), the last enzyme in the synthesis of melatonin, catalyzes N-acetylserotonin into melatonin. For the first time, we cloned ASMT from rice through the analysis of recombinant Escherichia coli harboring putative rice O-methyltransferase (OMT) cDNAs. In total, 18 full-length cDNA...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2010.00841.x
更新日期：2011-04-01 00:00:00
abstract：:A major goal of plant biotechnology is to improve the nutritional qualities of crop plants through metabolic engineering. Melatonin is a well-known bioactive molecule with an array of health-promoting properties, including potent antioxidant capability. To generate melatonin-rich rice plants, we first independently ov...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12120
更新日期：2014-04-01 00:00:00
abstract：:The circadian clock plays a vital role in physiology and behavior such as the sleep-wake cycle and blood pressure and hormone levels. Immune responses also display circadian rhythmicity and particularly pineal melatonin contributes to immunological processes. Little attention, however, is given to mechanisms underlyin...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12230
更新日期：2015-05-01 00:00:00
abstract：:Light and electron microscopic demonstrations for acid phosphatase (AcPase) activity in the chicken pineal gland were studied with special reference to the changes induced by the light-dark cycle. AcPase-positive lysosomes and Golgi cisternae and vesicles located in the pinealocyte in the light period are well develop...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1989.tb00407.x
更新日期：1989-01-01 00:00:00
abstract：:The effect of melatonin on thrombin-induced [3H]-arachidonic acid (AA) metabolism to cyclooxygenase derivatives was determined in platelets obtained from normal volunteers at 0830 and 2030 h. Percent conversion of radioactive AA was generally greater at 2030 h than at 0830 h for every cyclooxygenase derivative analyze...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1991.tb00465.x
更新日期：1991-10-01 00:00:00
abstract：:Female Syrian hamsters were kept in a light (14:10 h light:dark cycle, lights on 0600 h)- and temperature (22 or 30 degrees C)-controlled room; some groups were treated with an afternoon s.c. injection of melatonin (6.25, 12.5, or 25 micrograms/day) for 11 or 14 weeks. The melatonin-induced suppression of the reproduc...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1988.tb00656.x
更新日期：1988-01-01 00:00:00
abstract：:A decrease in nocturnal serum melatonin levels was reported in patients with clinically uncharacterized coronary artery disease. To assess whether there was a correlation between melatonin production and disease stage, we measured the nocturnal urinary excretion of 6-sulphatoxymelatonin (an index of blood melatonin co...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1034/j.1600-079x.2000.290302.x
更新日期：2000-10-01 00:00:00
abstract：:The effect of melatonin injection on Freund's adjuvant-induced changes in levels and 24-hr rhythms of circulating ACTH, growth hormone (GH), prolactin (PRL), luteinizing hormone (LH), and insulin was assessed in rats. Animals received subcutaneous (s.c.) injections of melatonin (30 microg) or vehicle, 1 hr before ligh...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1999.tb00592.x
更新日期：1999-08-01 00:00:00
abstract：:N-[2-(6-methoxyquinazolin-4-yl)-ethyl] acetamide (MQA) is a compound formed from the melatonin metabolite N(1)-acetyl-5-methoxykynuramine (AMK). We followed MQA production in reaction systems containing various putative reaction partners, in the absence and presence of hydrogen peroxide and/or copper(II). Although MQA...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2009.00723.x
更新日期：2010-01-01 00:00:00
abstract：:A physiologically based model of arousal dynamics is improved to incorporate the effects of the light spectrum on circadian phase resetting, melatonin suppression, and subjective sleepiness. To account for these nonvisual effects of light, melanopic irradiance replaces photopic illuminance that was used previously in ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12681
更新日期：2020-10-01 00:00:00
abstract：:An important role for melatonin in bone formation and restructuring has emerged, and studies demonstrate the multiple mechanisms for these beneficial actions. Statistical analysis shows that even with existing osteoporotic therapies, bone-related disease, and mortality are on the rise, creating a huge financial burden...
journal_title：Journal of pineal research
pub_type： 杂志文章,评审
doi：10.1111/jpi.12116
更新日期：2014-03-01 00:00:00
abstract：:The purpose of this study was to determine and compare the effects of chronic melatonin treatment in vivo on several aspects of prolactin (PRL) cell activity (PRL synthesis, storage, and release) in vitro in male and female Syrian hamsters. Adult male and female hamsters were maintained on long photoperiod and treated...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1989.tb00446.x
更新日期：1989-01-01 00:00:00
abstract：:Four-week-old male hamsters, born and raised in total darkness or in LD 14:10 (hr) were exposed to several low levels of illumination for 14 weeks. Analyses showed that testicular weights were significantly affected by both photic history and illuminance levels. Animals born in the dark possessed larger testes than th...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1985.tb00641.x
更新日期：1985-01-01 00:00:00
abstract：:Melatonin, a neurohormone that binds to two G protein-coupled receptors MT1 and MT2, is involved in pain regulation, but the distinct role of each receptor has yet to be defined. We characterized the nociceptive responses of mice with genetic inactivation of melatonin MT1 (MT1-/- ), or MT2 (MT2-/- ), or both MT1 /MT2 ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12671
更新日期：2020-10-01 00:00:00
abstract：:The objective of this study was to determine the role of alpha-adrenoceptors in melatonin production by rat pineal gland. Pineal glands were isolated from adult male rats and maintained in organ baths. The perfusate was sampled every 5 min, stored, and later assayed for melatonin. Exposure to norepinephrine (10 microM...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1034/j.1600-079x.2002.01842.x
更新日期：2002-05-01 00:00:00
abstract：:Melatonin is a very potent and efficient endogenous radical scavenger. The pineal indolamine reacts with the highly toxic hydroxyl radical and provides on-site protection against oxidative damage to biomolecules within every cellular compartment. Melatonin acts as a primary non-enzymatic antioxidative defense against ...
journal_title：Journal of pineal research
pub_type： 杂志文章,评审
doi：10.1111/j.1600-079x.1993.tb00498.x
更新日期：1993-05-01 00:00:00
abstract：:The pineal hormone melatonin, due to its lipophilic nature, has access to every cell and every part of a cell in the body, suggesting that it could exert effects on blood immune cells. The regulation of the activation of monocytes may be important in a number of diseases, especially pathophysiological conditions assoc...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1999.tb00566.x
更新日期：1999-01-01 00:00:00
