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Bcl-2 protein inhibitors

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https://www.readbyqxmd.com/read/29789637/the-proton-pump-inhibitor-pantoprazole-disrupts-protein-degradation-systems-and-sensitizes-cancer-cells-to-death-under-various-stresses
#1
Yu Cao, Min Chen, Dehua Tang, Hongli Yan, Xiwei Ding, Fan Zhou, Mingming Zhang, Guifang Xu, Weijie Zhang, Shu Zhang, Yuzheng Zhuge, Lei Wang, Xiaoping Zou
Proton pump inhibitors (PPIs) play a role in antitumor activity, with studies showing specialized impacts of PPIs on cancer cell apoptosis, metastasis, and autophagy. In this study, we demonstrated that pantoprazole (PPI) increased autophagosomes formation and affected autophagic flux depending on the pH conditions. PPI specifically elevated SQSTM1 protein levels by increasing SQSTM1 transcription via NFE2L2 activation independent of the specific effect of PPI on autophagic flux. Via decreasing proteasome subunits expression, PPI significantly impaired the function of the proteasome, accompanied by the accumulation of undegraded poly-ubiquitinated proteins...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29789603/vorinostat-and-quinacrine-have-synergistic-effects-in-t-cell-acute-lymphoblastic-leukemia-through-reactive-oxygen-species-increase-and-mitophagy-inhibition
#2
Bo Jing, Jin Jin, Rufang Xiang, Meng Liu, Li Yang, Yin Tong, Xinhua Xiao, Hu Lei, Wei Liu, Hanzhang Xu, Jiong Deng, Li Zhou, Yingli Wu
Despite recent progress in the treatment, the outcome of adult acute T-cell lymphoblastic leukemia (T-ALL) is poor. Development of novel approach to combat this disease is urgently required. Vorinostat, a pan-histone deacetylase (HDAC) inhibitor, exerts promising anticancer activity in a variety of solid and hematologic malignancies. However, the efficacy of vorinostat monotherapy is unsatisfactory. Here, we show that quinacrine (QC), an anti-malaria drug with potent autophagy inhibitory activity, could synergistically enhance vorinostat-induced cell death at a non-toxic concentration...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29787771/inhibition-of-pten-protects-pc12-cells-against-oxygen-glucose-deprivation-induced-cell-death-through-mitoprotection
#3
Fereshteh Farajdokht, Gisou Mohaddes, Elham Karimi-Sales, Taiebeh Kafshdooz, Javad Mahmoudi, Seyed Mohsen Aberoumandi, Pouran Karimi
Mitochondria involve in the determination of ischemic neuronal cell fate through regulation of apoptotic and necrotic cell death. Phosphatase and tensin homolog (PTEN) protein negatively regulates Akt/PKB signaling which is the major cell survival pathway. The current study aimed to examine the impact of SF1670, a potent PTEN inhibitor, on mitochondria-mediated cell survival pathways in an in vitro stroke-like model. PC12 cells were exposed to one hour oxygen and glucose deprivation (OGD) followed by different time points of reperfusion (0, 30, 60, 120 and 180 min) and SF1670 treatments...
May 19, 2018: Brain Research
https://www.readbyqxmd.com/read/29781034/specific-inhibitor-of-notch%C3%A2-3-enhances-the-sensitivity-of-nsclc-cells-to-gemcitabine
#4
Bi-Dan Hu, Jia Guo, Yuan-Zi Ye, Ting Du, Chun-Song Cheng, Qian Jiang, Ruo-Nan Liu, Yan-Bei Zhang
Notch‑3 is a receptor of the Notch signaling pathway and plays an important role in regulating self‑renewal, differentiation and apoptosis in cancer cells. Overexpression of Notch‑3 has been proved to be associated with resistance to gemcitabine (GEM) and poor patient prognosis for various malignant tumors. In the present study, two non‑small cell lung cancer (NSCLC) cell lines, H1299 and A549, were induced with GEM for two months and then were treated with various concentrations of a Notch signaling blocker, N‑[N‑(3,5‑difluorophenacetyl)‑L‑alanyl]‑S‑phenylglycine t‑butyl ester (DAPT), with the goal of reducing expression of Notch intracellular domain 3 (NICD3)...
May 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29777330/down-regulating-il-6-gp130-targets-improved-the-anti-tumor-effects-of-5-fluorouracil-in-colon-cancer
#5
Sanhong Li, Jilai Tian, Hongming Zhang, Shoubing Zhou, Xiyong Wang, Lei Zhang, Jiapeng Yang, Zhigang Zhang, Zhenling Ji
Recent studies have confirmed that IL-6/GP130 targets are closely associated with tumor growth, metastasis and drug resistance. 5-Fluorouracil (5-FU) is the most common chemotherapeutic agent for colon cancer but is limited due to chemoresistance and high cytotoxicity. Bazedoxifene (BZA), a third-generation selective estrogen receptor modulator, was discovered by multiple ligand simultaneous docking and drug repositioning approaches to have a novel function as an IL-6/GP130 target inhibitor. Thus, we speculated that in colon cancer, the anti-tumor efficacy of 5-FU might be increased in combination with IL-6/GP130 inhibitors...
May 18, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29777163/evolution-of-cll-treatment-from-chemoimmunotherapy-to-targeted-and-individualized-therapy
#6
REVIEW
Jan A Burger, Susan O'Brien
During the past 5 years, a number of highly active novel agents, including kinase inhibitors targeting BTK or PI3Kδ, an antagonist of the antiapoptotic protein BCL-2, and new anti-CD20 monoclonal antibodies, have been added to the therapeutic armamentarium for patients with chronic lymphocytic leukaemia (CLL). In these exciting times, care is needed to optimally integrate these novel agents into the traditional treatment algorithm without overlooking or compromising the benefits of established treatments, especially chemoimmunotherapy...
May 18, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29772677/lambertianic-acid-sensitizes-non-small-cell-lung-cancers-to-trail-induced-apoptosis-via-inhibition-of-xiap-nf-%C3%AE%C2%BAb-and-activation-of-caspases-and-death-receptor-4
#7
Deok Soo Ahn, Hyo Jung Lee, Jisung Hwang, Hyukgyu Han, Bonglee Kim, BumSang Shim, Sung-Hoon Kim
Lambertianic acid (LA) is a biologically active compound from the leaves of Pinus koraiensis. In the present study, apoptotic mechanisms of LA plus TNF-related apoptosis-inducing ligand (TRAIL) were elucidated in non-small cell lung cancer cells (NSCLCs). Cytotoxicity assay, flow cytometry, immunoprecipitation, and Western blotting were performed. Here, combined treatment of LA and TRAIL increased cytotoxicity, sub-G1 population, cleaved poly (ADP-ribose) polymerase (PARP), and caspase3/8/9 in A549 and H1299 cells compared to LA or TRAIL alone...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29772537/maternal-deprivation-promotes-hippocampal-neuronal-apoptosis-via-erk1-2-signaling
#8
Min Chen, Guoping He, Qiang Li
Neonatal maternal deprivation (MD) leads to depressive-like behaviors by promoting hippocampal neuronal apoptosis, but whether and how ERK1/2 signaling participates in MD-induced hippocampal neuronal apoptosis remains unclear. We therefore explored the role of ERK1/2 signaling pathway in neonatal MD-induced depression. Neonatal rats were divided into control group, PD group given intraperitoneal injections of MAPKK inhibitor (PD98059), MD group, and MD+PD group. The neonatal MD model was confirmed by behavioral tests...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29770817/the-dietary-compound-luteolin-inhibits-pancreatic-cancer-growth-by-targeting-bcl-2
#9
Zhimei Li, Yiyuan Zhang, Lixia Chen, Hua Li
Overexpression of the prosurvival protein BCL-2 contributes to malignant cell initiation, progression and resistance to treatment. Agents that function as its natural antagonists targeting BCL-2 must provide therapeutic benefit. In SW1990 pancreatic cancer cells, amplified BCL-2 was observed, which was believed to offer advantages for malignant cell survival and lead to poor patient outcome. Using structure-based virtual ligand screening, luteolin was found to be a natural small-molecule inhibitor of BCL-2, which exhibited dose-response proapoptosis activity in a BCL-2 dependent manner in vitro...
May 17, 2018: Food & Function
https://www.readbyqxmd.com/read/29770336/epigallocatechin-3-gallate-reduces-neuronal-apoptosis-in-rats-after-middle-cerebral-artery-occlusion-injury-via-pi3k-akt-enos-signaling-pathway
#10
Wang Nan, Xu Zhonghang, Chen Keyan, Liu Tongtong, Guo Wanshu, Xu Zhongxin
Background/Aims: Epigallocatechin-3-gallate (EGCG) has neuroprotective effects and the ability to resist amyloidosis. This study observed the protective effect of EGCG against neuronal injury in rat models of middle cerebral artery occlusion (MCAO) and investigated the mechanism of action of PI3K/AKT/eNOS signaling pathway. Methods: Rat models of permanent MCAO were established using the suture method. Rat behavior was measured using neurological deficit score. Pathology and apoptosis were measured using HE staining and TUNEL...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29767257/bmp%C3%A2-6-protects-retinal-pigment-epithelial-cells-from-oxidative-stress%C3%A2-induced-injury-by-inhibiting-the-mapk-signaling-pathways
#11
Li Chen, Ming Liu, Yan Luan, Yingfei Liu, Zhichao Zhang, Bo Ma, Xuan Liu, Yong Liu
Worldwide, neovascular age‑related macular degeneration (nAMD) is one of the most common causes of blindness in the elderly. In particular, degeneration of retinal pigment epithelial (RPE) cells represents the main pathological process in the development of nAMD, and oxidative stress serves a major role. The present study aimed to investigate the association between bone morphogenetic protein 6 (BMP‑6) and nAMD. BMP‑6 concentration was significantly reduced in patients with wet nAMD compared with in the control group...
May 14, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29767250/diosmetin-suppresses-human-prostate-cancer-cell-proliferation-through-the-induction-of-apoptosis-and-cell-cycle-arrest
#12
Christine Oak, Ahmad O Khalifa, Ilaha Isali, Natarajan Bhaskaran, Ethan Walker, Sanjeev Shukla
Diosmetin, a plant flavonoid, has been shown to exert promising effects on prostate cancer cells as an anti‑proliferative and anticancer agent. In this study, using western blot analysis for protein expression and flow cytometry for cell cycle analysis, we determined that the treatment of the LNCaP and PC‑3 prostate cancer cells with diosmetin resulted in a marked decrease in cyclin D1, Cdk2 and Cdk4 expression levels (these proteins remain active in the G0‑G1 phases of the cell cycle). These changes were accompanied by a decrease in c-Myc and Bcl-2 expression, and by an increase in Bax, p27Kip1 and FOXO3a protein expression, which suggests the potential modulatory effects of diosmetin on protein transcription...
May 16, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29767235/inhibition-of-microrna%C3%A2-16-protects-mesenchymal-stem-cells-against-apoptosis
#13
Jiang Rui, Shaohong Fang, Yongchen Wang, Bo Lv, Bo Yu, Shufeng Li
Bone marrow‑derived mesenchymal stem cells (BM‑MSCs) have been used in experimental research and clinical trials for heart function restoration and cardiomyocyte regeneration. However, due to a hostile microenvironment created by ischemia, hypoxia and pro‑inflammatory factors, the survival rate of implanted BM‑MSCs remains low. Therefore, strategies that can promote BM‑MSC survival and prevent apoptosis are required. Previous studies have reported that microRNA‑16 (miR‑16) can inhibit cell proliferation by targeting several proteins and signal pathway, not only by inducing apoptosis...
May 11, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29765528/metabolic-changes-associated-with-metformin-potentiates-bcl-2-inhibitor-venetoclax-and-cdk9-inhibitor-bay1143572-and-reduces-viability-of-lymphoma-cells
#14
Vineela Chukkapalli, Leo I Gordon, Parameswaran Venugopal, Jeffrey A Borgia, Reem Karmali
Metformin exerts direct anti-tumor effects by activating AMP-activated protein kinase (AMPK), a major sensor of cellular metabolism in cancer cells. This, in turn, inhibits pro-survival mTOR signaling. Metformin has also been shown to disrupt complex 1 of the mitochondrial electron transport chain. Here, we explored the lymphoma specific anti-tumor effects of metformin using Daudi (Burkitt), SUDHL-4 (germinal center diffuse large B-cell lymphoma; GC DLBCL), Jeko-1 (Mantle-cell lymphoma; MCL) and KPUM-UH1 (double hit DLBCL) cell lines...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29762835/microrna-520a-3p-inhibits-cell-growth-and-metastasis-of-non-small-cell-lung-cancer-through-pi3k-akt-mtor-signaling-pathway
#15
X Lv, C-Y Li, P Han, X-Y Xu
OBJECTIVE: MicroRNAs are a class of small non-coding RNAs that be involved in the pathogenesis of non-small cell lung cancer (NSCLC). The purpose of this study was to evaluate the effects of miR-520a-3p in cell growth and metastasis. MATERIALS AND METHODS: The mimics and inhibitor of miR-520a-3p were used to identify the effects of miR-520a-3p on cell proliferation and apoptosis using methylthiazol tetrazolium (MTT) assay and flow-cytometric method, respectively...
April 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29761903/the-combination-of-a-sphingosine-kinase-2-inhibitor-abc294640-and-a-bcl-2-inhibitor-abt-199-displays-synergistic-anti-myeloma-effects-in-myeloma-cells-without-a-t-11-14-translocation
#16
Pasupathi Sundaramoorthy, Cristina Gasparetto, Yubin Kang
Multiple myeloma (MM) remains an incurable disease in need of the development of novel therapeutic agents and drug combinations. ABT-199 is a specific Bcl-2 inhibitor in clinical trials for MM; however, its activity as a single agent was limited to myeloma patients with the t(11;14) translocation who acquire resistance due to co-expression of Mcl-1 and Bcl-xL. These limitations preclude its use in a broader patient population. We have recently found that a sphingosine kinase 2-specific inhibitor (ABC294640) induces apoptosis in primary human CD138+ cells and MM cell lines...
May 15, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29758299/autophagy-regulates-apoptosis-by-targeting-noxa-for-degradation
#17
Jingchao Wang, Danrui Cui, Shanshan Gu, Xiaoyu Chen, Yanli Bi, Xiufang Xiong, Yongchao Zhao
Apoptosis and autophagy mutually regulate various cellular physiological and pathological processes. The crosstalk between autophagy and apoptosis is multifaceted and complicated. Elucidating the molecular mechanism of their crosstalk will advance the therapeutic applications of autophagy for treating cancer and other diseases. NOXA, a BH3-only member of the BCL-2 family, was reported to induce apoptosis and promote autophagy. Here, we report that autophagy regulates apoptosis by targeting NOXA for degradation...
May 11, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29754474/oxymatrine-causes-hepatotoxicity-by-promoting-the-phosphorylation-of-jnk-and-induction-of-endoplasmic-reticulum-stress-mediated-by-ros-in-lo2-cells
#18
Li-Li Gu, Zhe-Lun Shen, Yang-Lei Li, Yi-Qi Bao, Hong Lu
Oxymatrine (OMT) often used in treatment for chronic hepatitis B virus infection in clinic. However, OMT-induced liver injury has been reported. In this study, we aim to investigate the possible mechanism of OMT-induced hepatotoxicity in human normal liver cells (L02). Exposed cells to OMT, the cell viability were decreased and apoptosis rate increased, the intracellular markers of oxidative stress were changed. Simultaneously, OMT altered apoptotic related proteins levels, including Bcl-2, Bax and pro-caspase-8/-9/-3...
May 10, 2018: Molecules and Cells
https://www.readbyqxmd.com/read/29752433/palmitic-acid-but-not-high-glucose-induced-myocardial-apoptosis-is-alleviated-by-n%C3%A2-acetylcysteine-due-to-attenuated-mitochondrial-derived-ros-accumulation-induced-endoplasmic-reticulum-stress
#19
Yang He, Lingyun Zhou, Zhiqiang Fan, Shikun Liu, Weijin Fang
Pharmacological inhibition of reactive oxygen species (ROS) is a potential strategy to prevent diabetes-induced cardiac dysfunction. This study was designed to investigate precise effects of antioxidant N‑acetylcysteine (NAC) in alleviating diabetic cardiomyopathy (DCM). Echocardiography and histologic studies were performed 12 weeks after streptozocin injection. Protein levels involved in endoplasmic reticulum stress (ERS) and apoptosis were analyzed by western blotting in diabetic hearts or high-glucose (HG, 30 mM)- and palmitic acid (PA, 300 μM)-cultured neonatal rat cardiomyocytes (NRCMs)...
May 11, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29750888/adiponectin-enhances-biological-functions-of-vascular-endothelial-progenitor-cells-through-the-mtor-stat3-signaling-pathway
#20
Xiaoying Dong, Xia Yan, Wei Zhang, Shengqiu Tang
Adiponectin (APN), an adipose tissue-excreted adipokine, plays protective roles in metabolic and cardiovascular diseases. In this study, the effects and mechanisms of APN on biological functions of rat vascular endothelial progenitor cells (VEPCs) were investigated in vitro. After administrating APN in rat VEPCs, the proliferation was measured by methyl thiazolyl tetrazolium (MTT) method, the apoptotic rate was test by Flow cytometry assay, mRNA expression of B-cell lymphoma-2 (Bcl-2) and vascular endothelial growth factor (VEGF) was determined by Real-time reverse transcriptase polymerase chain reaction (RT-PCR), and protein expression of mechanistic target of rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT3) and phospho-STAT3 (pSTAT3) was analyzed by Western Blot...
May 10, 2018: Physiological Research
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