Effects of metformin on proliferation and apoptosis of human megakaryoblastic Dami and MEG-01 cells.

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 Sci

authors

Liang X,Kong P,Wang J,Xu Y,Gao C,Guo G

doi

10.1016/j.jphs.2017.08.003

subject

Has Abstract

pub_date

2017-09-01 00:00:00

pages

14-21

issue

1

eissn

1347-8613

issn

1347-8648

pii

S1347-8613(17)30114-7

journal_volume

135

pub_type

杂志文章
  • Characteristics of attenuating effects of rebamipide, an anti-ulcer agent, on oxidative burst of human neutrophils.

    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

    doi:10.1254/jphs.91.153

    authors: Shimoyama T,Fukuda S,Liu Q,Fukuda Y,Nakaji S,Sugawara K

    更新日期:2003-02-01 00:00:00

  • Lipopolysaccharide- and glutamate-induced hypothalamic hydroxyl radical elevation and fever can be suppressed by N-methyl-D-aspartate-receptor antagonists.

    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

    doi:10.1254/jphs.fp0070272

    authors: Kao CH,Kao TY,Huang WT,Lin MT

    更新日期:2007-06-01 00:00:00

  • Involvement of endothelin and ET(A) endothelin receptor in mechanical allodynia in mice given orthotopic melanoma inoculation.

    abstract::We investigated whether endothelin (ET) would be involved in skin cancer pain in mice. Orthotopic inoculation of B16-BL6 melanoma cells into the plantar region of the hind paw produced marked mechanical allodynia in C57BL/6 mice. Intraplantar injections of the ET(A)-receptor antagonist BQ-123 (0.3 - 3 nmol/site), but ...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.fp0072051

    authors: Fujita M,Andoh T,Saiki I,Kuraishi Y

    更新日期:2008-02-01 00:00:00

  • Lifestyle-related diseases of the digestive system: a new in vitro model of hepatitis C virion production: application of basic research on hepatitis C virus to clinical medicine.

    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

    doi:10.1254/jphs.fm0070040

    authors: Saito S,Heller T,Yoneda M,Takahashi H,Nakajima A,Liang JT

    更新日期:2007-10-01 00:00:00

  • Pyrrolidine dithiocarbamate reduces vascular prostanoid-induced responses in aged type 2 diabetic rat model.

    abstract::It has been shown that enhancement of vasoconstrictor prostanoids plays an important role in the development of cardiovascular diseases. The aim of the present study was to examine the effects of pyrrolidine dithiocarbamate (PDTC), a low-molecular-weight thiol antioxidant and a potent inhibitor of nuclear factor-kappa...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.09116fp

    authors: Matsumoto T,Ishida K,Kobayashi T,Kamata K

    更新日期:2009-07-01 00:00:00

  • Establishment and characterization of mammalian cell lines stably expressing human L-type amino acid transporters.

    abstract::System L (SL), a basolateral amino acid transporter, transports large neutral amino acids (LNAAs) in a Na(+)-independent manner. Previously, we identified two isoforms of transporters: L-type amino acid transporter 1 (LAT1) and 2 (LAT2) and revealed their distinct substrate selectivity and transport properties. In thi...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.08232fp

    authors: Morimoto E,Kanai Y,Kim DK,Chairoungdua A,Choi HW,Wempe MF,Anzai N,Endou H

    更新日期:2008-12-01 00:00:00

  • QT PRODACT: usability of miniature pigs in safety pharmacology studies: assessment for drug-induced QT interval prolongation.

    abstract::To investigate whether miniature pigs are useful for evaluating the potential of drugs for drug-induced prolongation of the QT interval, we performed an in vivo QT assay using conscious and unrestricted miniature pigs. Compared with the vehicle average baseline values, haloperidol at 3 and 10 mg/kg, p.o. prolonged the...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.qt-c13

    authors: Kano M,Toyoshi T,Iwasaki S,Kato M,Shimizu M,Ota T

    更新日期:2005-01-01 00:00:00

  • Possible involvement of endogenous opioid system located downstream of α7 nicotinic acetylcholine receptor in mice with physical dependence on nicotine.

    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

    authors: Ueno K,Kiguchi N,Kobayashi Y,Saika F,Wakida N,Yamamoto C,Maeda T,Ozaki M,Kishioka S

    更新日期:2014-01-01 00:00:00

  • Neuroprotective effects of methyl 3,4-dihydroxybenzoate against H₂O₂-induced apoptosis in RGC-5 cells.

    abstract::In the present study, we investigated the protective effect of methyl 3,4-dihydroxybenzoate (MDHB) against H2O2-induced apoptosis in RGC-5 cells. The RGC-5 cells were cultured in plates for 24 h, which were then pretreated with dimethyl sulfoxide, different concentrations of MDHB, or probucol for 12 h prior to additio...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.13055fp

    authors: Zhou X,Su CF,Zhang Z,Wang CY,Luo JQ,Zhou XW,Cai L,Yan L,Zhang W,Luo HM

    更新日期:2014-01-01 00:00:00

  • The inhibitory mechanism of YC-1, a benzyl indazole, on smooth muscle cell proliferation: an in vitro and in vivo study.

    abstract::The pharmacological mechanisms of a synthetic compound 1-benzyl-3-(5'-hydroxymethyl-2'-furyl) indazole (YC-1) in preventing smooth muscle cell proliferation remains to be elucidated. The present study was aimed to explore the effects of YC-1 on certain molecules responsible for cell proliferation, including transformi...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.94.252

    authors: Wu CH,Chang WC,Chang GY,Kuo SC,Teng CM

    更新日期:2004-03-01 00:00:00

  • Entecavir as a P2X7R antagonist ameliorates platelet activation and thrombus formation.

    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

    authors: Ming Y,Xin G,Ji B,Ji C,Wei Z,Zhang B,Zhang J,Yu K,Zhang X,Li S,Li Y,Xing Z,Niu H,Huang W

    更新日期:2020-09-01 00:00:00

  • Myelin-related gene silencing mediated by LPA1 - Rho/ROCK signaling is correlated to acetylation of NFκB in S16 Schwann cells.

    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

    authors: Tsukahara R,Ueda H

    更新日期:2016-10-01 00:00:00

  • Modifications of capsaicin-sensitive neurons in isolated guinea pig ileum by [6]-gingerol and lafutidine.

    abstract::A segment of guinea pig ileum was used to confirm the hypothesis that [6]-gingerol and lafutidine interact with capsaicin-sensitive neurons. Addition of 30 and 100 microM [6]-gingerol (a pungent constituent of ginger) induced contraction of the ileum immediately. Like capsaicin, [6]-gingerol-induced contraction was in...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.92.359

    authors: Someya A,Horie S,Yamamoto H,Murayama T

    更新日期:2003-08-01 00:00:00

  • TRPV4-like non-selective cation currents in cultured aortic myocytes.

    abstract::In this study, we provide evidence of critical changes in the expression of non-selective cation currents (NSCC) during culture in rat aortic myocytes. A selective TRPV4 agonist, 4alpha-phorbol 12,13-didecanoate (4alphaPDD), had little effect on membrane currents and intracellular Ca(2+) (Ca(2+)(i)) in freshly isolate...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.08133fp

    authors: Tanaka R,Muraki K,Ohya S,Yamamura H,Hatano N,Itoh Y,Imaizumi Y

    更新日期:2008-10-01 00:00:00

  • Negative impact of anesthesia with midazolam, sufentanil, and propofol used in pediatric flexible bronchoscopy on the tracheal ciliary beat frequency in guinea pigs.

    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

    authors: Joskova M,Durdik P,Sutovska M,Grendar M,Koniar D,Hargas L,Banovcin P,Franova S

    更新日期:2020-04-01 00:00:00

  • Effects of some antipsychotics and a benzodiazepine hypnotic on the sleep-wake pattern in an animal model of schizophrenia.

    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

    authors: Ishida T,Obara Y,Kamei C

    更新日期:2009-09-01 00:00:00

  • Roles of β- and α2-adrenoceptors within the central nucleus of the amygdala in the visceral pain-induced aversion in rats.

    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

    authors: Deyama S,Takishita A,Tanimoto S,Ide S,Nakagawa T,Satoh M,Minami M

    更新日期:2010-01-01 00:00:00

  • Forced exercise-induced flushing of tail skin in ovariectomized mice, as a new experimental model of menopausal hot flushes.

    abstract::Hot flushes are the most common complaint of menopausal women. In the present study, a new animal model of hot flushes was established. Tail skin temperature was measured with a thermo tracer after mice were subjected to a forced exercise task using a motor driven treadmill. In ovariectomized mice, forced exercise for...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.sc0050046

    authors: Shuto H,Yamauchi A,Ikeda M,Sohda Y,Koga A,Tominaga K,Egawa T,Kataoka Y

    更新日期:2005-07-01 00:00:00

  • Effect of histamine on muscimol-induced working memory deficits in radial maze performance.

    abstract::We investigated the participation of gamma-aminobutyric acid (GABA) neurons of the medial septal area in eight-arm radial maze performance in rats. The intra-septal injection of muscimol, a GABA(A) agonist, caused an increase in total error and working memory error. On the other hand, no significant effect was observe...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.fp0061472

    authors: Yamamoto Y,Mikami A,Fujii Y,Kamei C

    更新日期:2007-07-01 00:00:00

  • Possible involvement of β₁ receptors in various emetogen-induced increases in salivary amylase activity in rats.

    abstract::We investigated the inhibitory effects of β₁- or β₂-adrenoceptor (AR) antagonists on salivary amylase secretion produced by various emetic agents, such as cisplatin, apomorphine, and lithium chloride (LiCl), or the non-emetic agent β(½)-AR agonist isoprenaline in rats. We also determined the inhibitory effect of metoc...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.10265fp

    authors: Fukui H,Suyama Y,Iwachido T,Miwa E

    更新日期:2011-01-01 00:00:00

  • Estrogenic compound attenuates angiotensin II-induced vascular smooth muscle cell proliferation through interaction between LKB1 and estrogen receptor α.

    abstract::The prevalence rate of cardiovascular disease is higher for males than females, and estradiol (E2) induces AMP-activated protein kinase (AMPK) activation, which is known to regulate proliferation of VSMC. We identified the estrogenic properties of nordihydroguaiaretic acid (NDGA, a lignan phytoestrogen) that inhibit V...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1016/j.jphs.2016.09.001

    authors: Kim SA,Lee KY,Kim JR,Choi HC

    更新日期:2016-09-01 00:00:00

  • Lig-8, a bioactive lignophenol derivative from bamboo lignin, protects against neuronal damage in vitro and in vivo.

    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

    authors: Ito Y,Shimazawa M,Akao Y,Nakajima Y,Seki N,Nozawa Y,Hara H

    更新日期:2006-10-01 00:00:00

  • Diazepam Enhances Production of Diazepam-Binding Inhibitor (DBI), a Negative Saliva Secretion Regulator, Localized in Rat Salivary Gland.

    abstract::Peripheral-type benzodiazepine receptor (PBR) and central-type benzodiazepine receptor (CBR) in salivary gland play a role in the inhibitory regulation of salivary secretion in rodents. Diazepam-binding inhibitor (DBI), an endogenous ligand for PBR, produces neurosteroids, which modulate CBR activity. In this study, w...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.10282FP

    authors: Tsukagoshi E,Kawaguchi M,Shinomiya T,Yoshikawa M,Kawano T,Okubo M,Sawaki K

    更新日期:2011-01-01 00:00:00

  • Linkage between coenzyme a metabolism and inflammation: roles of pantetheinase.

    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

    doi:10.1254/jphs.13r01cp

    authors: Nitto T,Onodera K

    更新日期:2013-09-20 00:00:00

  • How do acupuncture and moxibustion act? - Focusing on the progress in Japanese acupuncture research -.

    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

    authors: Kawakita K,Shinbara H,Imai K,Fukuda F,Yano T,Kuriyama K

    更新日期:2006-01-01 00:00:00

  • Combination treatment of perifosine and valsartan showed more efficiency in protecting against pressure overload induced mouse heart failure.

    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

    authors: Li WJ,Liao HH,Feng H,Zhou ZY,Mou SQ,Zhang N,Wu HM,Xia H,Tang QZ

    更新日期:2020-07-01 00:00:00

  • The antipsychotic and antiemetic drug prochlorperazine delays the ventricular repolarization of the in situ canine heart.

    abstract::Electropharmacological effect of the antipsychotic and antiemetic drug prochlorperazine was assessed using the halothane-anesthetized in vivo canine model (n = 5). Up to 10 times higher than the clinically relevant doses of prochlorperazine (< or = 3 mg/kg, i.v.) did not induce cardiohemodynamic collapse in the model....

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.fpj04038x

    authors: Satoh Y,Sugiyama A,Takahara A,Ando K,Wang K,Honsho S,Hashimoto K

    更新日期:2005-01-01 00:00:00

  • The role of muscarinic receptor subtypes on carbachol-induced contraction of normal human detrusor and overactive detrusor associated with benign prostatic hyperplasia.

    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

    authors: Yamanishi T,Kaga K,Fuse M,Shibata C,Kamai T,Uchiyama T

    更新日期:2015-06-01 00:00:00

  • Long-lasting anti-emetic effect of T-2328, a novel NK(1) antagonist.

    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

    authors: Watanabe Y,Okamoto M,Ishii T,Takatsuka S,Taniguchi H,Nagasaki M,Saito A

    更新日期:2008-06-01 00:00:00

  • On the mechanisms underlying histamine induction of gastric mucosal lesions in rats with partial gastric vascular occlusion.

    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

    authors: Amagase K,Okabe S

    更新日期:2003-06-01 00:00:00