Abstract:
:Deregulated cancer cell metabolism plays an important role in cancer progression. Cancer cell metabolism has been in the centre of attention in therapeutical cancer cell targeting. Repurposed chemical agents, such as metformin and aspirin, have been studied extensively as preventive and therapeutic agents. Metformin is Food and Drug administration (FDA)-approved antidiabetic drug cheaper than other chemotherapeutic agents that were shown to have anticancer effects. Memantine is an FDA-approved Alzheimer's drug. Drug repositioning studies offer wide range of benefits, such as reduced time, cost and risk over de novo drug discovery. Therefore, we aimed to target glucose and glutamine metabolism in androgen-dependent LNCaP cells by using metformin and memantine and investigate these agents' effects on prostate cancer cell proliferation in vitro. We evaluated the effects of metformin and memantine on the protein expression levels of genes that play significant roles in apoptosis and cell cycle progression (Casp3, Casp9, Bcl-2, Survivin, Bax, c-Myc, HIF1A, CCND1, CDK4 and GAPDH) by Western blotting. Alzheimer's drug memantine exerted cytotoxic effects at 0.25 mM and metformin at 2.5 mM. We identified for the first time that memantine exerts antineoplastic activity (0.25 mM) by triggering Bax-dependent pathway of apoptosis. In addition to that both molecules have shown similar patterns on pro- and anti-apoptotic protein expression levels, such as Bcl-2, Casp3, Survivin and Bax. Our preclinic results indicate that memantine might be used as a new repositioned drug in cancer treatment. Beyond targeting glucose metabolism, glutamine metabolism also holds great promise for a potential treatment option.
journal_name
Hum Exp Toxicoljournal_title
Human & experimental toxicologyauthors
Albayrak G,Konac E,Dikmen AU,Bilen CYdoi
10.1177/0960327117747025subject
Has Abstractpub_date
2018-09-01 00:00:00pages
953-958issue
9eissn
0960-3271issn
1477-0903journal_volume
37pub_type
杂志文章abstract::Trichothecenes are mycotoxins produced by various species of fungi which can occur on various agricultural products. Among these compounds, T-2 toxin, HT-2 toxin, diacetoxyscirpenol (DAS) and deoxynivalenol (DON) are the most naturally encountered and potent trichothecenes. Consumption of trichothecene contaminated fo...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/096032719701601108
更新日期:1997-11-01 00:00:00
abstract::Paraquat (PQ) is a highly toxic herbicide that is used in most of the countries without restriction. The cytotoxic effect of PQ is mediated by radicals, which are the products of PQ reduction in cells. The anti-oxidative action of captopril, an angiotensin-converting enzyme inhibitor, appears to be through its ability...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327107084533
更新日期:2007-10-01 00:00:00
abstract::Until quite recently, pentabromodiphenyl ether (PentaBDE) was most commonly used as a flame retardant. Due to the considerably long atmospheric half-life of PentaBDE and its contribution to environmental pollution, it is categorized as a persistent organic pollutant (POP). As the data on the toxicity of PentaBDE is ra...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327110371261
更新日期:2011-05-01 00:00:00
abstract::The color of the teeth is an important topic for many people and can be influenced by intrinsic and extrinsic stains. There is an increasing demand for whitening of the teeth year by year. The most popular way of whitening is "bleaching," which is the result of the breakdown of pigments located in the enamel and/or th...
journal_title:Human & experimental toxicology
pub_type: 临床试验,杂志文章
doi:10.1177/0960327118817103
更新日期:2019-04-01 00:00:00
abstract::This study was designed to investigate the effect of agmatine sulfate (AG, CAS2482-00-0) in nicotine (NIC)-induced vascular endothelial dysfunction (VED) in rabbits. NIC was administered to produce VED in rabbits with or without AG for 6 weeks. Serum lipid profile, serum thiobarbituric acid reactive substances, reduce...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327115597311
更新日期:2016-05-01 00:00:00
abstract:AIM:Diazinon (DZN) is one of the most important organophosphorus compounds used to control pests in agriculture in many countries. Several studies have shown that exposure to DZN may alter protein expression in the liver. In order to further investigate the mechanism of DZN toxicity, differentially expressed ATP-intera...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327115619771
更新日期:2016-10-01 00:00:00
abstract::1. The effect of pyridostigmine on cardiorespiratory function after oxime + atropine injection was investigated in tabun poisoned guinea-pigs and without tabun poisoning. 2. The trachea, a carotid artery and jugular vein were cannulated in female urethane-anaesthetised Pirbright-white guinea-pigs. After baseline measu...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/096032719501400803
更新日期:1995-08-01 00:00:00
abstract::This study was designed to determine the levels of prolactin, leptin, osteopontin, and follistatin in workers chronically and subacutely exposed to lead compounds. The examined population consisted of three groups. The first group was composed of 56 male workers who were chronically exposed to lead for 13.38 ± 10.38 y...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327116658106
更新日期:2017-06-01 00:00:00
abstract::This study deals with pesticide exposure profile in some European countries with a specific focus on ethylenebisdithiocarbamates (EBDC). In all, 55 Bulgarian greenhouse workers, 51 Finnish potato farmers, 48 Italian vineyard workers, 42 Dutch floriculture farmers, and 52 Bulgarian zineb producers entered the study. Ea...
journal_title:Human & experimental toxicology
pub_type: 杂志文章,多中心研究
doi:10.1177/0960327108100003
更新日期:2008-09-01 00:00:00
abstract::The phenomenon of subtoxic stimulation of organism response is not uncommon in aquatic toxicology experiments. We describe the presence of hormesis in both growth and reproduction experiments in aquatic toxicology where these responses are observed in both animals and plants and at different trophic levels of an ecosy...
journal_title:Human & experimental toxicology
pub_type: 杂志文章,评审
doi:10.1177/096032719801700505
更新日期:1998-05-01 00:00:00
abstract::Experimental studies have shown that prenatal exposure to lead (Pb) produces morphological changes related to extracellular matrix remodelling. To analyse whether the matrix metalloproteinases (MMPs), particularly MMP-2, MMP-9, and the tissue inhibitor of metalloproteinases-2 (TIMP-2), are associated with morphologica...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327111431706
更新日期:2012-07-01 00:00:00
abstract::1. In humans morphine is metabolised to morphine-3-glucuronide (M3G) which possess no opioid activity, and morphine-6-glucuronide (M6G) which is a potent opioid receptor agonist that probably contribute to the desired as well as toxic effects of morphine. 2. In order to investigate the possible effect of ranitidine on...
journal_title:Human & experimental toxicology
pub_type: 临床试验,杂志文章
doi:10.1177/096032719801700611
更新日期:1998-06-01 00:00:00
abstract::We have investigated the pituitary-testicular axis in a well-characterized population which was occupationally exposed to mercury vapour. Thyroid stimulating hormone and prolactin were also measured as indices of thyroid and pituitary endocrine function. We found no relation between blood or urine mercury levels or le...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/096032719101000309
更新日期:1991-05-01 00:00:00
abstract::Sulfur mustard (SM) represents a potential chemical warfare agent. In order to characterize SM-induced airway epithelial damage, we studied the effects of an intratracheal injection of 0.3 mg/kg of SM in guinea pigs, 5 h, 24 h, 14 days and 35 days after exposure. During the acute period, lesions prevailed in tracheal ...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/096032719601501204
更新日期:1996-12-01 00:00:00
abstract::Serrapeptase (SP) and nattokinase (NK) are proteolytic enzymes belonging to serine proteases. In this study, we hypothesized that SP and NK could modulate certain factors that are associated with Alzheimer's disease (AD) pathophysiology in the experimental model. Oral administration of aluminium chloride (AlCl3) in a ...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327112467040
更新日期:2013-07-01 00:00:00
abstract::This study was designed to evaluate the hepato and neuroprotective activity of Daflon and low-dose γ radiation on thioacetamide (TAA)-induced liver damage and hepatic encephalopathy (HE) in rats. Effect of daily Daflon treatment (100 mg/kg body weight, Per OS (p.o.) for consecutive 3 days) and/or fractionated low-dose...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327116637657
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Diphenhydramine (DPHM) overdose is a frequent cause of acute poisoning. Although its clinical features are well known, information about the dose-dependent toxicity of DPHM is still scarce. The objective of this study was to investigate the dose-dependent toxicity of DPHM in patients with acute DPHM poisonin...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1191/096032700671040438
更新日期:2000-09-01 00:00:00
abstract::Naringenin is a naturally occurring flavanones and has been found to exhibit free radical scavenging, enzyme inhibition, antioxidants, anti-inflammatory, and anticancer activities. Present study was designed to evaluate the protective role of naringenin against benzo[a]pyrene (B[a]P)-induced oxidative stress and pulmo...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327116650009
更新日期:2017-04-01 00:00:00
abstract::1. The methods used to evaluate the toxicological effects of PCBs in animals have been reviewed. 2. The data show that Toxic Equivalency Factors (TEFs) could be developed to assess the potential toxicity of PCB mixtures for certain specific target organ effects (such as the liver and immune system) but would be inappr...
journal_title:Human & experimental toxicology
pub_type: 杂志文章,评审
doi:10.1177/096032719401300901
更新日期:1994-09-01 00:00:00
abstract::The study was done to find out whether subacute exposure to supercypermethrin forte (SCM) affected cellular and humoral immunity. Groups of 10 male Wistar rats were given SCM by gavage for 28 days at 12.5 mg kg-1 day-1 (1/14 LD50), 8.75 mg kg-1 day-1 (1/20 LD50) and 4.38 mg kg-1 day-1 (1/40 LD50) and the response of s...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/096032719501400502
更新日期:1995-05-01 00:00:00
abstract::1-Bromopropane (1-BP) is an increasingly used chemical solvent for cleaning metals and gradually replacing spraying adhesives. Workers exposed to 1-BP (WBP) showed nervous system dysfunction and other symptoms. This study focused on the proteomic change between healthy individuals (HIs), WBP and poisoned patients with...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327117689911
更新日期:2018-01-01 00:00:00
abstract::1. Four different concentrations of quinalphos and methyl parathion were tested on human peripheral lymphocytes over different time periods, for the analysis of chromosomal aberrations and sister chromatid exchanges (SCEs). 2. A significant increase in chromosomal aberrations was observed when cells were treated with ...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/096032719000900605
更新日期:1990-11-01 00:00:00
abstract::In the 1980s, villages in the Kurdistan region of Iraq were exposed to chemical weapons (CWs), which killed and injured thousands of civilians. There has been no clinical assessment of the long-term effects of CWs exposure on those injured. We report the first such evaluation of CW effects on long-term health of child...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327117734620
更新日期:2018-08-01 00:00:00
abstract::Endogenous alcohol has been applied for spontaneous ethanol production via different metabolic pathways of the human body. Auto-brewery syndrome describes the patients with alcohol intoxication after ingesting carbohydrate-rich meals. The main objective of this study is to investigate the effect of diabetes mellitus (...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327116661400
更新日期:2017-05-01 00:00:00
abstract::Two previously healthy women developed nausea, vomiting, headache and dizziness for several days, a massive hair loss about 2 weeks later and a discoloration of the fingernails. Detailed diagnostic procedures did not reveal any pathological results. Therapeutic measures did not show any effect. Thallium and arsenic we...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327109360046
更新日期:2010-05-01 00:00:00
abstract::The aim of the present study was to investigate whether cognitive behavioral impairment, induced by nicotine in offspring rats, was associated with the alteration of hippocampal short-term potentiation (STP) and long-term potentiation (LTP) and to discuss the potential underlying mechanism. Young adult offspring rats ...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327113494902
更新日期:2014-02-01 00:00:00
abstract::Phagocytes remove and store mercury (Hg) that enters the body. Macrophages and granulocytes respond in opposite ways to Hg: macrophages loose cell viability, and neutrophils become protected from apoptosis. We have investigated the cytology of early intake of Hg by macrophages and neutrophils after a short period (2-4...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1191/0960327104ht472oa
更新日期:2004-08-01 00:00:00
abstract::1. Multiple low doses of the direct acting organophosphates, ecothiopate, paraoxon and mipafox produced persistent and additive inhibition of diaphragm acetylcholinesterase. Paraoxon and mipafox had similar effects on brain acetylcholinesterase. There was greater recovery from inhibition between doses for paraoxon and...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/096032719701600201
更新日期:1997-02-01 00:00:00
abstract::Kampo (Japanese traditional herbal) medicines have been produced by combining multiple crude drugs, almost all of plant origin but with some of animal or mineral origin, and contain a great many substances. Their effect is a combination of the various interactions of the constituent substances, whether they are enhanc...
journal_title:Human & experimental toxicology
pub_type: 杂志文章,评审
doi:10.1191/0960327106het654oa
更新日期:2006-08-01 00:00:00
abstract::Severe carbon monoxide (CO) poisoning causes fulminant deaths in common environment as well as neurological sequelae to survivors. Prevention of delayed neurological syndrome (DNS) after exposure to CO, the most important sequela, is based up to date on hyperbaric oxygen administration. Nevertheless, its use remains c...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327120901572
更新日期:2020-06-01 00:00:00