Abstract:
:Metformin has received increasing attention for its potential anticancer activity against certain human leukemia cells, but its effects on human megakaryoblastic cells are unclear. This study aimed to investigate the effects of metformin on proliferation and apoptosis of human megakaryoblastic cells (Dami and MEG-01) and the underlying molecular mechanisms. CCK8 assay was employed to measure cell proliferation. Flow cytometry was adopted to detect cell apoptosis. Western blot was further employed to measure apoptosis-related proteins. In Dami and MEG-01 cells, metformin significantly inhibited proliferation and promoted apoptosis in a dose- and time-dependent manner, and metformin (4 mM) was selected for subsequent experiments. Metformin inhibited ERK1/2, JNK, and PI3K/Akt, but activated p38 pathway in these two cells. Moreover, inhibition of ERK1/2, JNK or PI3K/Akt pathway alone induced cell apoptosis compared to the control group. The combination of specific inhibitors of ERK1/2, JNK or PI3K/Akt pathway and metformin further promoted cell apoptosis and the up-regulation of p21, Bax, Bad, cleaved caspase-3 and -9 as well as the down-regulation of Bcl-2 mediated by metformin alone, but inhibition of p38 pathway exhibited the opposite results. These findings support the possibility of metformin treatment as a new therapeutic strategy against acute megakaryoblastic leukemia (AMKL).
journal_name
J Pharmacol Scijournal_title
Journal of pharmacological sciencesauthors
Liang X,Kong P,Wang J,Xu Y,Gao C,Guo Gdoi
10.1016/j.jphs.2017.08.003subject
Has Abstractpub_date
2017-09-01 00:00:00pages
14-21issue
1eissn
1347-8613issn
1347-8648pii
S1347-8613(17)30114-7journal_volume
135pub_type
杂志文章abstract::The aim of this study was to characterize the effects of rebamipide on the oxidative burst of human neutrophils. The neutrophil oxidative burst was measured in the presence of rebamipide and cimetidine using lucigenin- or luminol-dependent chemiluminescence (LgCL or LmCL). Rebamipide inhibited the LmCL response stimul...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
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abstract::The purpose of the current study was to explore the effects of N-methyl-D-aspartate (NMDA)-receptor antagonists (MK-801 and LY235959) administered intracerebroventricularly on the changes of both core temperature and hypothalamic levels of 2,3-dihydroxybenzoic acid (2,3-DHBA) induced by intracerebroventricular injecti...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
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journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.fp0072051
更新日期:2008-02-01 00:00:00
abstract::The hepatitis C virus (HCV) is an enveloped virus with a single positive-strand RNA genome of about 9.6 kb. It is a major cause of liver disease worldwide. Clear understanding of the viral life cycle has been hampered by the lack of a robust cell culture system. While the development of the HCV replicon system was a m...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章,评审
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journal_title:Journal of pharmacological sciences
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doi:10.1254/jphs.09116fp
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journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.08232fp
更新日期:2008-12-01 00:00:00
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journal_title:Journal of pharmacological sciences
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doi:10.1254/jphs.qt-c13
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abstract::We previously reported that nicotine (NIC)-induced analgesia was elicited in part by activation of the endogenous opioid system. Moreover, it is well known that NIC has physical-dependence liability, but its mechanism is unclear. Therefore, we examined whether physical dependence on NIC was mediated by activation of t...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.13172fp
更新日期:2014-01-01 00:00:00
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journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.13055fp
更新日期:2014-01-01 00:00:00
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abstract::Platelet activation is the primary cause of thrombosis. The P2X7 receptor (P2X7R) is a therapeutic target of thrombosis. However, it is still unknown whether P2X7R activation affects platelet thrombus. Our molecular docking results showed that entecavir as a P2X7R antagonist interacted perfectly with the human P2X7R (...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.jphs.2020.07.002
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abstract::Lysophosphatidic acid (LPA) initiates demyelination following peripheral nerve injury, which causes neuropathic pain. Our previous in vivo and ex vivo studies using mice have demonstrated that LPA-induced demyelination of spinal dorsal roots is attributed by the LPA1-type receptor-mediated down-regulation of myelin-re...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.jphs.2016.07.010
更新日期:2016-10-01 00:00:00
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journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.92.359
更新日期:2003-08-01 00:00:00
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journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.08133fp
更新日期:2008-10-01 00:00:00
abstract::There is no direct evidence for the exact cilia-inhibitory effects of opioids, which are generally used to achieve general anesthesia in combination with other anesthetic drugs. These are the reasons, why we analysed direct concentration-dependent or systemic effects of anesthetics (propofol, sufentanil, and midazolam...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.jphs.2020.01.005
更新日期:2020-04-01 00:00:00
abstract::We studied the effects of antipsychotics and a hypnotic on sleep disturbance in schizophrenia using an animal model of the disease. Electrodes for the electroencephalogram (EEG) and electromyogram (EMG) were chronically implanted into the cortex and the dorsal neck muscle of rats. EEG and EMG were recorded with an ele...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.09142fp
更新日期:2009-09-01 00:00:00
abstract::We investigated the roles of β- and α(2)-adrenoceptors within the central nucleus of the amygdala (CeA) in the negative affective and sensory components of visceral pain in rats. We observed a dose-dependent reduction of intraperitoneal acetic acid-induced conditioned place aversion by bilateral injections of timolol,...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.10139sc
更新日期:2010-01-01 00:00:00
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journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.sc0050046
更新日期:2005-07-01 00:00:00
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doi:10.1254/jphs.fp0061472
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journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.10265fp
更新日期:2011-01-01 00:00:00
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journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.jphs.2016.09.001
更新日期:2016-09-01 00:00:00
abstract::Lig-8, a lignophenol derivative from bamboo lignin, potently suppresses oxidative stress-induced apoptosis. Here, we first examined in vitro whether lig-8 protects against neuronal damage induced by oxygen-glucose deprivation (OGD) followed by reoxygenation, tunicamycin [endoplasmic reticulum (ER)-stress inducer], or ...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.fp0060711
更新日期:2006-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1254/jphs.10282FP
更新日期:2011-01-01 00:00:00
abstract::Pantetheinase is an enzyme hydrolyzing pantetheine, an intermediate of the coenzyme A degradation pathway. Pantetheinase has long been considered as the enzyme that recycles pantothenic acid (vitamin B5) generated during coenzyme A breakdown. Genetic analyses showed that mammals have multiple genes known as vanin fami...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章,评审
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更新日期:2013-09-20 00:00:00
abstract::The mechanisms of action of acupuncture and moxibustion as reported by Japanese researchers are reviewed. The endogenous opioid-mediated mechanisms of electroacupuncture (EA) as used in China are well understood, but these are only one component of all mechanisms of acupuncture. These studies emphasize the similarity ...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1254/jphs.crj06004x
更新日期:2006-01-01 00:00:00
abstract::The optimum strategy for heart failure (HF) treatment has yet to be elucidated. This study intended to test the benefit of a combination of valsartan (VAL) and perifosine (PER), a specific AKT inhibitor, in protecting against pressure overload induced mouse HF. Mouse were subjected to aortic banding (AB) surgery to es...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.jphs.2020.04.001
更新日期:2020-07-01 00:00:00
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journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
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更新日期:2005-01-01 00:00:00
abstract::The aim of this study was to compare the effect of antimuscarinic antagonists on carbachol-induced contraction of normal human bladder and detrusor overactivity associated with benign prostatic hyperplasia (DO/BPH). Samples of human bladder muscle were obtained from patients undergoing total cystectomy for bladder can...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.jphs.2015.05.005
更新日期:2015-06-01 00:00:00
abstract::The effect of T-2328 {2-fluoro-4'-methoxy-3'-[[[(2S,3S)-2-phenyl-3-piperidinyl]amino]methyl]-[1,1'-biphenyl]-4-carbonitrile dihydrochloride}, a novel tachykinin NK(1)-receptor antagonist, was examined on cisplatin-induced emesis in ferrets. Cisplatin induced acute emesis in 24 h and delayed emesis during 24 and 72 h, ...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.08027fp
更新日期:2008-06-01 00:00:00
abstract::Although it is well known that histamine induces gastric mucosal lesions in laboratory animals, the fundamental mechanisms remain unclear. In order to further analyze the vascular mechanisms underlying histamine-induced lesions, a new model was developed in the glandular stomach via administration of histamine (40 mg/...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.92.124
更新日期:2003-06-01 00:00:00