Abstract:
AIMS:Histone deacetylase inhibitors (HDACis) are promising anticancer drugs that open new areas of epigenetic drug discovery. Multiple myeloma (MM) is a malignant tumor of the blood system that is difficult to cure and often relapses. Here, we investigated the in vitro effects of a novel HDACi, LMK-235, on MM cells, and explored the underlying mechanisms. MAIN METHODS:Real-time PCR and western blot were used to measure the expression of HDAC4 and HO-1 in MM cells treated with LMK-235. si-RNA was used to transfect MM cells. Hemin or ZnPP was combined to regulate heme oxygenase-1 (HO-1), and a pathway inhibitor was added to measure changes in the JNK/AP-1 signaling pathway. Apoptosis and proliferation were assessed by flow cytometry and CCK-8 assay, respectively. KEY FINDINGS:We found that LMK-235, a selective inhibitor of class IIA HDAC4/5, induced apoptosis of MM cells by downregulating HO-1 that is closely related to HDAC4. LMK-235 increased phosphorylation of JNK and c -Jun in MM cells. Downregulation of HO-1 expression in combination with LMK-235 expression further activated phosphorylation of JNK and c-Jun and induced apoptosis in MM cells. When the JNK inhibitor SP600125 was used in combination, the apoptosis phenomenon was reversed. However, when HO-1 was upregulated, LMK-235-mediated phosphorylation of JNK and c-Jun was inhibited, and apoptosis of MM cells began to decrease. SIGNIFICANCE:These data suggest that LMK-235 has potent anti-myeloma activity through regulation of HO-1-induced apoptosis via the JNK/AP-1 pathway. This provides a new concept for the treatment of multiple myeloma.
journal_name
Life Scijournal_title
Life sciencesauthors
Li X,Guo Y,Kuang X,Zhao L,Li H,Cheng B,Wang W,Zhang Z,Liu P,Wang Jdoi
10.1016/j.lfs.2019.03.011subject
Has Abstractpub_date
2019-04-15 00:00:00pages
146-157eissn
0024-3205issn
1879-0631pii
S0024-3205(19)30169-9journal_volume
223pub_type
杂志文章相关文献
LIFE SCIENCES文献大全abstract::Superoxide dismutase (SOD), neuron specific enolase (NSE) and lactic dehydrogenase (LDH) were measured in the serum and cerebrospinal fluid (CSF) of ischemic cerebrovascular patients, other neurological patients and in age-matched healthy controls (serum only). The levels of SOD in the CSF or serum of the ischemic pat...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(94)90159-7
更新日期:1994-01-01 00:00:00
abstract::In adult male Wistar rats submitted to a standardized noise stress, intravenous TRH induced a prolactin (PRL) secretory response. Prior IV naloxone administration not only lowered plasma PRL levels in those stressed rats but abolished also the stimulatory action of TRH. This effect was further studied by superfusion e...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(87)90756-9
更新日期:1987-06-22 00:00:00
abstract:AIMS:Enhanced aerobic glycolysis is an essential hallmark of malignant cancer. Blocking the glycolytic pathway has been suggested as a therapeutic strategy to impair the proliferation of tumor cells. Metformin, a widely used anti-diabetes drug, exhibits anti-tumor properties. However, the underlying molecular mechanism...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/j.lfs.2019.116966
更新日期:2019-12-15 00:00:00
abstract::Epidemiological studies have shown that cigarette smoke, an oxidant agent, is a risk factor for the development of diabetic nephropathy (DN), in which pathogenesis transforming growth factor beta(1) (TGFbeta(1)) plays a key role. In our experimental model we exposed mesangial cell cultures to cigarette smoke concentra...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/j.lfs.2003.12.026
更新日期:2004-06-18 00:00:00
abstract::The initial stage of atherosclerotic plaque formation involves oxidation of the phosphatidyl-choline moiety of low density lipoprotein (LDL) and subsequent uptake by macrophages. Ongoing uptake in developing plaque also may involve oxidized LDL and would require an oxidizing environment in plaque lipids. Atherosclerot...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(95)02351-8
更新日期:1996-01-01 00:00:00
abstract::According to recent epidemiological reports, almost 40% of American population use complimentary and alternative medicine (CAM) during their lifetime. Patients detected with HIV or cancer often consume herbal products especially St. John's wort (SJW) for antidepressants in combination with prescription medicines. Such...
journal_title:Life sciences
pub_type: 杂志文章,评审
doi:10.1016/j.lfs.2005.12.010
更新日期:2006-03-27 00:00:00
abstract::Bile duct ligation (BDL) in rats induces portal fibrosis. This process has been linked to changes in the oxidative state of the hepatic cells and in the production of nitric oxide. Our objective was to find possible temporal connections between hepatic redox state, NO synthesis and liver injury. In this work we have c...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/j.lfs.2004.01.017
更新日期:2004-06-25 00:00:00
abstract::The objective of the present study was to investigate the roles of protein kinase A and/or C in agonist-induced beta adrenoceptor activation in intact human lymphocytes. LYmphocytes from healthy subjects were incubated with isoproterenol and phosphodiesterase inhibitor (IBMX, 1.0 mM) after 20 minutes of preincubation ...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(90)90584-e
更新日期:1990-01-01 00:00:00
abstract::Individuals have an inherent capacity to cope with stressors in the form of stress adaptation. Apart from stress adaptation there is another well documented phenomenon known as cross stress adaptation. In this, there is a reduction in stress responsiveness to a novel stressor (in which the adapted organism had never e...
journal_title:Life sciences
pub_type: 杂志文章,评审
doi:10.1016/j.lfs.2015.07.018
更新日期:2015-09-15 00:00:00
abstract::Kappa (kappa) opioid agonists induce a water diuresis and inhibit vasopressin (AVP) secretion. Hypothalamic and neurohypophysial sites have both been implicated in the response. The present study was designed to ascertain if kappa-agonist inhibition of osmotically-stimulated AVP secretion is associated with parallel c...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/s0024-3205(97)00931-4
更新日期:1997-01-01 00:00:00
abstract::In our previous studies, exposure of mice to millimeter waves (MW) increased the duration of anesthesia caused by either ketamine or chloral hydrate, and this effect was blocked by naloxone. To further characterize the biological effects of MW, we have chosen a new animal model of experimental itch. Male Swiss albino ...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/s0024-3205(98)00436-6
更新日期:1998-01-01 00:00:00
abstract:AIMS:We explored the effect of aerobic exercise on renal sinus adipose (RSA) accumulation and RSA accumulation-related renal injury in obese mice. MAIN METHODS:C57BL/6J male mice (n = 30) were evenly divided into three groups: control group (CON, n = 10), obese group (OB, n = 10; given high-fat diet) and obese + aerob...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/j.lfs.2021.119106
更新日期:2021-01-23 00:00:00
abstract::MicroRNAs plays important role in the development of myocardial infarction (MI). The aim of this study was to analyze whether miR-429 has effect on the process of autophagy in myocardial anoxia/reoxygenation (AR) or ischemia/reperfusion (IR) injury and explore the underlying mechanism. The results showed that miR-429 ...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/j.lfs.2019.116842
更新日期:2019-10-15 00:00:00
abstract::Formation of etretinate, ethyl ester of acitretin, can be confirmed in vitro and in vivo using acitretin as the substrate. Etretinate was identified by LC/MS. The in vitro incubation was performed using rat and human liver 12,000 g supernatant, and the in vivo experiment was conducted in rats after oral dosing of acit...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(91)90332-6
更新日期:1991-01-01 00:00:00
abstract::1,25-dihydroxyvitamin D3 has important physiological effects such as calcium transport and cell growth and differentiation. These biological effects are mediated by their binding to specific intracellular receptor termed vitamin D receptor (VDR). VDR mRNA expression has been demonstrated in several tissues, but to dat...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/s0024-3205(96)00586-3
更新日期:1997-01-01 00:00:00
abstract:AIMS:The pulmonary vasodilation induced by adrenomedullin may be beneficial in the acute pulmonary embolism (APE) setting. This study examined effects of adrenomedullin in sheep with microsphere-induced APE. MAIN METHODS:Twenty four anesthetized, mechanically ventilated sheep were randomly assigned into 3 groups (n=8 ...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/j.lfs.2015.08.013
更新日期:2015-10-15 00:00:00
abstract::The anticonvulsant activity of U-54494A was studied in a 4-aminopyridine (4-AP) epilepsy model using extracellular recordings in in vitro hippocampal slices. Field potentials were evoked by stimulation of Schaffer collaterals, and recorded from the CA1 region of the hippocampus after infusion of 4-AP in the absence an...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(92)90381-x
更新日期:1992-01-01 00:00:00
abstract::The effect of exogenous ascorbic acid intake on biosynthesis of ascorbic acid in mice has been studied. After the mice were on diets containing added ascorbic acid for two months, the activities of ascorbic acid synthesizing enzymes in the mouse liver homogenates were measured using L-gulono-gamma-lactone as a substra...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(89)90421-9
更新日期:1989-01-01 00:00:00
abstract::Respiratory performance, heart rate and blood pressure were studied in halothane anesthetized rats after administration of taurine and the putative taurine antagonist 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1, 1-dioxide hydrochloride (TAG). Intracerebroventricular (i.c.v.) taurine depressed ventilation due to...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(83)90720-8
更新日期:1983-10-24 00:00:00
abstract::Female white-footed mice (Peromyscus leucopus) were injected twice daily with 5, 10, 50, 100 micrograms melatonin (MEL) or saline. Injections were given for 7 weeks at 2 and 12 hours after lights-on under a long day (LD 16:8) photoperiod. Afternoon administration of MEL induced gonadal regression, although a dose of 5...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(85)90549-1
更新日期:1985-08-26 00:00:00
abstract:AIMS:The potential of human mesenchymal stem cell-like stroma prepared from placental/umbilical cord blood for hematopoietic regeneration by X-irradiated hematopoietic stem cells is herein assessed. MAIN METHODS:Placental/umbilical cord blood-derived mesenchymal stem cell-like stromal cells were applied to a regenerat...
journal_title:Life sciences
pub_type: 杂志文章
doi:
更新日期:2009-04-24 00:00:00
abstract::The present study was designed to evaluate the suppressive effect of different frequencies of signaled-shock presentations on mitogenic reactivity of lymphocytes in Lewis rats, and to assess the recovery of that reactivity at varying times after the shocks. The results showed that the magnitude of decreased reactivity...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(87)90699-0
更新日期:1987-10-12 00:00:00
abstract::We evaluated the effects of FR901533, endothelin converting enzyme inhibitor, on development of right ventricular overload and medial thickening of pulmonary arteries in rats with monocrotaline-induced pulmonary hypertension. Pulmonary hypertension was induced by a single injection of monocrotaline (80 mg/kg). Twenty-...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/s0024-3205(98)00347-6
更新日期:1998-01-01 00:00:00
abstract::Viperid, elapid and crotalid snake venoms were screened in vitro for antiviral activity against Sendai virus. The hemolysis of 10(8) human erythrocytes in 1 ml, caused by 70 HAU of Sendai virus, was abolished when the virions were pretreated with 10 ug of the viperid venom of Echis coloratus, and was considerably dimi...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(92)90015-h
更新日期:1992-01-01 00:00:00
abstract::Effects of 1-methyl-4-phenylpyridine(MPP+), a putative neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP), on the contents of dopamine were examined in the various regions of the rat brain. Under anesthesia with pentobarbital sodium and flunitrazepam, MPP+ 150 micrograms/rat was intracerebrove...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(89)90625-5
更新日期:1989-01-01 00:00:00
abstract::Diabetes mellitus is a metabolic disorder in which the glucose level in blood exceeds beyond the normal level. Persistent hyperglycemia leads to diabetes late complication and obviously account for a large number of morbidity and mortality worldwide. Numerous therapeutic options are available for the treatment of diab...
journal_title:Life sciences
pub_type: 杂志文章,评审
doi:10.1016/j.lfs.2017.10.025
更新日期:2018-01-15 00:00:00
abstract::Voltage clamp recordings of GH3/B6 pituitary cells reveal the presence of non linear steady state membrane properties at the level of the resting potential (about -41 mV). Clamping the cells to potentials more depolarized than -60 mV is associated with a potential dependent increase in membrane conductance and membran...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(82)90475-1
更新日期:1982-05-31 00:00:00
abstract:AIMS:The antihypertensive mechanism (s) of the epigallocatechin-3-gallate (EGCG), a major effective component in green tea, might associate with microRNAs (miRNAs). Here, we aimed to investigate which microRNA in aorta of spontaneously hypertensive rats (SHRs) were modulated by administration of EGCG and its mechanism....
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/j.lfs.2018.04.041
更新日期:2018-06-15 00:00:00
abstract::The inhibitory activity of methylguanidine, guanidine and their precursors, creatine and creatinine, on both the neuronal constitutive and lung inducible isoforms of nitric oxide synthase were examined in this study. Methylguanidine and guanidine (0.01-3 mM) significantly (P<0.01) inhibited in a concentration-dependen...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/s0024-3205(97)00673-5
更新日期:1997-01-01 00:00:00
abstract::Nitric oxide (NO) is a potent regulator in the cardiovascular system; it is generated by the nitric oxide synthase (NOS) family of proteins. NO produced in endothelial cells plays a crucial role in vascular functions. The aim of this study was to clarify the effect of diabetes on aortic NO synthesis in a model of gene...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/j.lfs.2005.02.010
更新日期:2005-07-15 00:00:00