Memantine induces apoptosis and inhibits cell cycle progression in LNCaP prostate cancer cells.

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 Toxicol

authors

Albayrak G,Konac E,Dikmen AU,Bilen CY

doi

10.1177/0960327117747025

subject

Has Abstract

pub_date

2018-09-01 00:00:00

pages

953-958

issue

9

eissn

0960-3271

issn

1477-0903

journal_volume

37

pub_type

杂志文章
  • In vitro toxicity of trichothecenes on human erythroblastic progenitors.

    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

    authors: Rio B,Lautraite S,Parent-Massin D

    更新日期:1997-11-01 00:00:00

  • Hepatoprotective role of captopril on paraquat induced hepatotoxicity.

    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

    authors: Elmi A,Sadeghi Zh,Elmi S,Daraei B,Ghazi-Khansari M

    更新日期:2007-10-01 00:00:00

  • The effect of short-term intoxication of rats with pentabromodiphenyl ether (in mixture mimic commercial products).

    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

    authors: Bruchajzer E,Frydrych B,Sporny S,Szymańska JA

    更新日期:2011-05-01 00:00:00

  • Evaluation of biochemical changes in dental tissues after different office bleaching methods.

    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

    authors: Karaarslan ES,Özmen ZC,Aytac F,Bicakci AA,Buldur M,Aydogan L,Hologlu F,Özkocak B

    更新日期:2019-04-01 00:00:00

  • Effect of agmatine on experimental vascular endothelial dysfunction.

    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

    authors: Nader MA,Gamiel NM,El-Kashef H,Zaghloul MS

    更新日期:2016-05-01 00:00:00

  • Proteomics screening of adenosine triphosphate-interacting proteins in the liver of diazinon-treated rats.

    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

    authors: Pourtaji A,Robati RY,Lari P,Hosseinzadeh H,Ramezani M,Abnous K

    更新日期:2016-10-01 00:00:00

  • Effect of pyridostigmine pretreatment on cardiorespiratory function in tabun poisoning.

    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

    authors: Worek F,Kleine A,Szinicz L

    更新日期:1995-08-01 00:00:00

  • The influence of chronic and subacute exposure to lead on the levels of prolactin, leptin, osteopontin, and follistatin in humans.

    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

    authors: Dobrakowski M,Kasperczyk A,Czuba ZP,Machoń-Grecka A,Szlacheta Z,Kasperczyk S

    更新日期:2017-06-01 00:00:00

  • Biological monitoring and questionnaire for assessing exposure to ethylenebisdithiocarbamates in a multicenter European field study.

    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

    authors: Fustinoni S,Campo L,Liesivuori J,Pennanen S,Vergieva T,van Amelsvoort L,Bosetti C,Van Loveren H,Colosio C

    更新日期:2008-09-01 00:00:00

  • Incorporating hormesis in the routine testing of hazards.

    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

    authors: Bailer AJ,Oris JT

    更新日期:1998-05-01 00:00:00

  • Altered expressions of MMP-2, MMP-9, and TIMP-2 in placentas from women exposed to lead.

    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

    authors: González-Puebla E,González-Horta C,Infante-Ramírez R,Sanin LH,Levario-Carrillo M,Sánchez-Ramírez B

    更新日期:2012-07-01 00:00:00

  • Influence of ranitidine on the morphine-3-glucuronide to morphine-6-glucuronide ratio after oral administration of morphine in humans.

    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

    authors: Aasmundstad TA,Størset P

    更新日期:1998-06-01 00:00:00

  • Occupational mercury vapour exposure and testicular, pituitary and thyroid endocrine function.

    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

    authors: McGregor AJ,Mason HJ

    更新日期:1991-05-01 00:00:00

  • Airway epithelial damage induced by sulfur mustard in guinea pigs, effects of glucocorticoids.

    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

    authors: Calvet JH,Coste A,Levame M,Harf A,Macquin-Mavier I,Escudier E

    更新日期:1996-12-01 00:00:00

  • Serrapeptase and nattokinase intervention for relieving Alzheimer's disease pathophysiology in rat model.

    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

    authors: Fadl NN,Ahmed HH,Booles HF,Sayed AH

    更新日期:2013-07-01 00:00:00

  • Novel effect of Daflon and low-dose γ-radiation in modulation of thioacetamide-induced hepatic encephalopathy in male albino rats.

    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

    authors: Abdel-Rafei M,Amin MM,Hasan HF

    更新日期:2017-01-01 00:00:00

  • Dose-dependent toxicity of diphenhydramine overdose.

    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

    authors: Radovanovic D,Meier PJ,Guirguis M,Lorent JP,Kupferschmidt H

    更新日期:2000-09-01 00:00:00

  • Amelioration of Benzo[a]pyrene-induced oxidative stress and pulmonary toxicity by Naringenin in Wistar rats: A plausible role of COX-2 and NF-κB.

    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

    authors: Ali R,Shahid A,Ali N,Hasan SK,Majed F,Sultana S

    更新日期:2017-04-01 00:00:00

  • Review of the safety assessment of polychlorinated biphenyls (PCBs) with particular reference to reproductive toxicity.

    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

    authors: Battershill JM

    更新日期:1994-09-01 00:00:00

  • Investigation of immunotoxicity of supercypermethrin forte in the Wistar rat.

    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

    authors: Tulinská J,Kubová J,Janota S,Nyulassy S

    更新日期:1995-05-01 00:00:00

  • Large-scale label-free proteomics analysis of occupational poisoned patients of 1-bromopropane, workers exposed to 1-bromopropane and healthy individuals.

    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

    authors: Miao R,Ding B,Zhang Y,Zhao R,Li Y,Zhu B

    更新日期:2018-01-01 00:00:00

  • Cytogeneticity of quinalphos and methyl parathion in human peripheral lymphocytes.

    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

    authors: Rupa DS,Reddy PP,Reddi OS

    更新日期:1990-11-01 00:00:00

  • Long-term health effects of chemical warfare agents on children following a single heavy exposure.

    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

    authors: Talabani JM,Ali AI,Kadir AM,Rashid R,Samin F,Greenwood D,Hay A

    更新日期:2018-08-01 00:00:00

  • Auto-brewery syndrome: Ethanol pseudo-toxicity in diabetic and hepatic patients.

    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

    authors: Hafez EM,Hamad MA,Fouad M,Abdel-Lateff A

    更新日期:2017-05-01 00:00:00

  • Acute selenium poisoning by paradise nuts (Lecythis ollaria).

    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

    authors: Müller D,Desel H

    更新日期:2010-05-01 00:00:00

  • Nicotine-induced impairments of spatial cognition and long-term potentiation in adolescent male rats.

    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

    authors: Han G,An L,Yang B,Si L,Zhang T

    更新日期:2014-02-01 00:00:00

  • Mercury intake by inflammatory phagocytes: in vivo cytology of mouse macrophages and neutrophils by X-ray elemental microanalysis coupled with scanning electron microscopy.

    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

    authors: Cunha EM,Oliveira MJ,Ferreira PG,Aguas AP

    更新日期:2004-08-01 00:00:00

  • The effects of multiple low doses of organophosphates on target enzymes in brain and diaphragm in the mouse.

    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

    authors: Williams FM,Charlton C,de Blaquière GE,Mutch E,Kelly SS,Blain PG

    更新日期:1997-02-01 00:00:00

  • Pharmacology and toxicology of Bupleurum root-containing Kampo medicines in clinical use.

    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

    authors: Ikegami F,Sumino M,Fujii Y,Akiba T,Satoh T

    更新日期:2006-08-01 00:00:00

  • Current and research therapies for the prevention and treatment of delayed neurological syndrome associated with carbon monoxide poisoning: A narrative review.

    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

    authors: Del Moral-Barbudo B,Blancas R,Ballesteros-Ortega D,Quintana-Díaz M,Martínez-González Ó

    更新日期:2020-06-01 00:00:00