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Bcl-2 inhibitors

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https://www.readbyqxmd.com/read/29150734/the-sirtuin-1-2-inhibitor-tenovin-1-induces-a-nonlinear-apoptosis-inducing-factor-dependent-cell-death-in-a-p53-null-ewing-s-sarcoma-cell-line
#1
Christian Marx, Lisa Marx-Blümel, Nora Lindig, René Thierbach, Doerte Hoelzer, Sabine Becker, Susan Wittig, Roland Lehmann, Hortense Slevogt, Thorsten Heinzel, Zhao-Qi Wang, James F Beck, Jürgen Sonnemann
The sirtuin 1/2 inhibitor tenovin-1 activates p53 and may have potential in the management of cancer. Here, we investigated the responsiveness of Ewing's sarcoma cells to tenovin-1. We examined its effects in two Ewing's sarcoma cell lines with different p53 status, i.e. in p53 wild-type and p53 null cells. Effects were assessed by flow cytometric analyses of cell death, mitochondrial membrane depolarization and reactive oxygen species (ROS) generation, by caspase 3/7 activity measurement, by mRNA expression profiling and by immunoblotting...
November 18, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29149414/role-of-tctp-for-cellular-differentiation-and-cancer-therapy
#2
Ean-Jeong Seo, Nicolas Fischer, Thomas Efferth
The translationally controlled tumor protein (TCTP) is a highly conserved protein that is regulated due to a high number of extracellular stimuli. TCTP has an important role for cell cycle and normal development. On the other side, tumor reversion and malignant transformation have been associated with TCTP. TCTP has been found among the 12 genes that are differentially expressed during mouse oocyte maturation, and an overexpression of this gene was reported in a wide variety of different cancer types. Its antiapoptotic effect is indicated by the interaction with several proapoptotic proteins of the Bcl-2 family and the p53 tumor suppressor protein...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29142607/curcumin-inhibits-mcf-7-cells-by-modulating-the-nf-%C3%AE%C2%BAb-signaling-pathway
#3
Jun-Li Liu, Yan-Yan Pan, Ou Chen, Yun Luan, Xia Xue, Jing-Jie Zhao, Ling Liu, Hong-Ying Jia
The present study investigated the inhibitory effect of curcumin on human breast cancer MCF-7 cells and investigated the potential underlying molecular mechanisms. MCF-7 cells were cultured with curcumin at different concentrations and time points. The effects of curcumin treatment on breast cancer cell proliferation were studied using a MTT assay. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to assess the mRNA and protein expression levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax), nuclear factor-κ-light-chain-enhancer of activated B cells (NF-κB) and inhibitor of NF-κB-α (IκBα)...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29142404/chalepin-a-compound-from-ruta-angustifolia-l-pers-exhibits-cell-cycle-arrest-at-s-phase-suppresses-nuclear-factor-kappa-b-nf-%C3%AE%C2%BAb-pathway-signal-transducer-and-activation-of-transcription-3-stat3-phosphorylation-and-extrinsic-apoptotic-pathway-in-non-small-cell
#4
Jaime Stella Moses Richardson, Norhaniza Aminudin, Sri Nurestri Abd Malek
Background: Plants have been a major source of inspiration in developing novel drug compounds in the treatment of various diseases that afflict human beings worldwide. Ruta angustifolia L. Pers known locally as Garuda has been conventionally used for various medicinal purposes such as in the treatment of cancer. Objective: A dihydrofuranocoumarin named chalepin, which was isolated from the chloroform extract of the plant, was tested on its ability to inhibit molecular pathways of human lung carcinoma (A549) cells...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29139009/lfm-a13-a-potent-inhibitor-of-polo-like-kinase-inhibits-breast-carcinogenesis-by-suppressing-proliferation-activity-and-inducing-apoptosis-in-breast-tumors-of-mice
#5
Kazim Sahin, Mehmet Tuzcu, Mehmet Yabas, Cemal Orhan, Nurhan Sahin, Ibrahim H Ozercan
The goals of the present study were to define the anticancer activity of LFM-A13 (α-cyano-β-hydroxy-β-methyl-N-(2,5-dibromophenyl)-propenamide), a potent inhibitor of Polo-like kinase (PLK), in a mouse mammary cancer model induced by 7,12-dimethylbenz(a)anthracene (DMBA) in vivo and explore its anticancer mechanism(s). We also examined whether the inhibition of PLK by LFM-A13 would improve the efficiency of paclitaxel in breast cancer growth in vivo. To do this, female BALB/c mice received 1 mg of DMBA once a week for 6 weeks with oral gavage...
November 15, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29138985/effects-of-microrna-708-on-epithelial-mesenchymal-transition-cell-proliferation-and-apoptosis-in-melanoma-cells-by-targeting-lef1-through-the-wnt-signaling-pathway
#6
Xiao-Fei Song, Qi-Hua Wang, Ran Huo
This study was conducted in order to elucidate the role microRNA-708 (miR-708) plays between proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) involving melanoma cells by targeting using LEF1 through the Wnt signaling pathway. Male Kunming mice were selected and subsequently divided into normal and model groups to take part in this study. Following cell line selection, the B16 cells with the highest miR-708 expression were selected and assigned into the control, blank, negative control (NC), miR-708 mimic, miR-708 inhibitor, siRNA-LEF1, and miR-708 inhibitor + siRNA-LEF1 groups...
November 14, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29138357/tadalafil-a-long-acting-phosphodiesterase-inhibitor-promotes-bone-marrow-stem-cell-survival-and-their-homing-into-ischemic-myocardium-for-cardiac-repair
#7
Ibrahim Elmadbouh, Muhammad Ashraf
The aim was to evaluate the tadalafil-mediated effects at molecular level on bone marrow-derived mesenchymal stem cells (MSCs) survival and their homing into the infarcted hearts to promote cardiac repair and improve function. MSCs were pretreated in vitro with inhibitors of PKG, MAPK, FasL, nitric oxide synthase (NOS) (L-NAME), CXCR4 (AMD3100), or miR-21 inhibitors (+/-luciferase construction +/-Fas) prior to tadalafil treatment for 2 h. These MSCs were then subjected to H2O2 stress to assess their injury...
November 2017: Physiological Reports
https://www.readbyqxmd.com/read/29137527/binding-modes-of-bcl-2-homology-3-bh3-peptides-with-anti-apoptotic-protein-a1-and-redesign-of-peptide-inhibitors-a-computational-study
#8
Yantao Chen, Jun Wang, Jian Zhang, Wei Wang
The interaction between protein and peptide ligand is a challenging problem in molecular biology and drug design. The binding of the Bcl-2 homology 3 (BH3) peptide to the anti-apoptotic protein A1 was revealed as a critical step in the regulation of apoptosis. These BH3 peptides hold high structural similarity, but are diverse in their regulation abilities. Based on molecular simulations and MM-P(G)BSA methods, this work presented a detailed analysis on binding mechanism of the BH3 peptides derived from PUMA and BMF...
November 15, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29133058/design-and-synthesis-of-thienopyrimidine-urea-derivatives-with-potential-cytotoxic-and-pro-apoptotic-activity-against-breast-cancer-cell-line-mcf-7
#9
Eman F Abdelhaleem, Mohammed K Abdelhameid, Asmaa E Kassab, Manal M Kandeel
A series of novel tetrahydrobenzothieno[2,3-d]pyrimidine urea derivatives was synthesized according to fragment-based design strategy. They were evaluated for their anticancer activity against MCF-7 cell line. Three compounds 9c, 9d and 11b showed 1.5-1.03 folds more potent anticancer activity than doxorubicin. In this study, a promising multi-sited enzyme small molecule inhibitor 9c, which showed the most potent anti-proliferative activity, was identified. The anti-proliferative activity of this compound appears to correlate well with its ability to inhibit topoisomerase II (IC50 = 9...
October 28, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29132010/inhibition-of-sonic-hedgehog-signaling-blocks-cell-migration-and-growth-but-induces-apoptosis-via-suppression-of-foxq1-in-natural-killer-t-cell-lymphoma
#10
Pingyi Liu, Lingling Chen
The present study explored the effects of Forkhead box Q1 (FOXQ1) on cell proliferation, cell cycle and apoptosis via the Sonic hedgehog (Shh) pathway in Natural killer/T-cell lymphoma (NKTCL). Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to detect FOXQ1 expression in 117 NKTCL patients and 120 healthy controls. Additionally, FOXQ1 expression in NKTCL cell lines (HANK-1, NK-92, SNK-6, SNT-8 and YT) was determined by western blotting and qRT-PCR. SNK-6 cells were transfected with FOXQ1-shRNA or Shh pathway inhibitor Cyclopamine/recombinant protein Shh...
November 10, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29131030/n-cadherin-mediated-activation-of-pi3k-akt-gsk-3%C3%AE-signaling-attenuates-nucleus-pulposus-cell-apoptosis-under-high-magnitude-compression
#11
Pei Li, Zherui Liang, Gang Hou, Lei Song, Ruijie Zhang, Yibo Gan, Chengmin Zhang, Yichun Xu, Qiang Zhou
BACKGROUND/AIMS: Mechanical overloading-induced nucleus pulposus (NP) apoptosis plays an important role in the pathogenesis of intervertebral disc degeneration. N-cadherin (N-CDH)-mediated signaling preserves normal NP cell phenotype. This study aims to investigate the effects of N-CDH on NP cell apoptosis under high-magnitude compression and the underlying mechanism behind this process. METHODS: Rat NP cells seeded on scaffold were perfusion-cultured using a self-developed perfusion bioreactor for 5 days and experienced different magnitudes (2% and 20% compressive deformation, respectively) of compression at a frequency of 1...
November 9, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29129468/inhibition-of-rac1-ameliorates-neuronal-oxidative-stress-damage-via-reducing-bcl-2-rac1-complex-formation-in-mitochondria-through-pi3k-akt-mtor-pathway
#12
Yundan Pan, Na Wang, Pingping Xia, E Wang, Qulian Guo, Zhi Ye
Although the neuroprotective effects of Rac1 inhibition have been reported in various cerebral ischemic models, the molecular mechanisms of action have not yet been fully elucidated. In this study, we investigated whether the inhibition of Rac1 provided neuroprotection in a diabetic rat model of focal cerebral ischemia and hyperglycemia-exposed PC-12 cells. Intracerebroventricular administration of lentivirus expressing the Rac1 small hairpin RNA (shRNA) and specific Rac1 inhibitor NSC23766 not only decreased the infarct volumes and improved neurologic deficits with a correlated significant activation of mitochondrial DNA specific proteins, such as OGG1 and POLG, but also elevated Bcl-2 S70 phosphorylation in mitochondria...
November 10, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29119107/santamarine-inhibits-nf-%C3%AE%C2%BAb-activation-and-induces-mitochondrial-apoptosis-in-a549-lung-adenocarcinoma-cells-via-oxidative-stress
#13
Xuefeng Wu, Hua Zhu, Jingzhe Yan, Muhammad Khan, Xiuyan Yu
Santamarine (STM), a sesquiterpene lactone component of Magnolia grandiflora and Ambrosia confertiflora, has been shown to possess antimicrobial, antifungal, antibacterial, anti-inflammatory, and anticancer activities. However, no study has yet been conducted to investigate the molecular mechanism of STM-mediated anticancer activity. In the present study, we found that STM inhibits growth and induces apoptosis in A549 lung adenocarcinoma cells through induction of oxidative stress. STM induces oxidative stress by promoting reactive oxygen species (ROS) generation, depleting intracellular glutathione (GSH), and inhibiting thioredoxin reductase (TrxR) activity in a dose-dependent manner...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29118909/role-of-autophagy-and-its-signaling-pathways-in-ischemia-reperfusion-injury
#14
Shaohua Dai, Qirong Xu, Sheng Liu, Bentong Yu, Jichun Liu, Jian Tang
This study was conducted to investigate the mechanism of autophagy and its signaling pathways in ischemia/reperfusion injury (IRI). Pulmonary microvascular endothelial cells (PMVECs) were used to construct I/R models. The cells were then treated with autophagy inhibitor 3-MA and infected with adenovirus expressing Beclin 1-shRNA. The expression of CD31, LC3-II, Bcl-2, Bax, LC3-II, Beclin 1, AKT, p-AKT, AMPK and p-AMPK, apoptosis, cell viability and migration ability were determined. Over 95% isolated PMVECs were positive for CD31...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29118061/venetoclax-is-effective-in-small-cell-lung-cancers-with-high-bcl-2-expression
#15
Timothy L Lochmann, Konstantinos V Floros, Mitra Naseri, Krista M Powell, Wade Cook, Ryan J March, Giovanna T Stein, Patricia Greninger, Yuki Kato Maves, Laura R Saunders, Scott J Dylla, Carlotta Costa, Sosipatros A Boikos, Joel D Leverson, Andrew J Souers, Geoffrey W Krystal, Hisashi Harada, Cyril H Benes, Anthony C Faber
PURPOSE:  Small cell lung cancer (SCLC) is an often-fatal neuroendocrine carcinoma usually presenting as extensive disease, carrying a 3% five-year survival. Despite notable advances in SCLC genomics, new therapies remain elusive, largely due to a lack of druggable targets. EXPERIMENTAL DESIGN:  We used a high-throughput drug screen to identify a venetoclax sensitive SCLC sub-population, and validated the findings with multiple patient-derived xenografts of SCLC...
November 8, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29115607/schisandrin-b-protects-against-myocardial-ischemia-reperfusion-injury-via-the-pi3k-akt-pathway-in-rats
#16
Xuyong Zhao, Yijia Xiang, Changhong Cai, Aiming Zhou, Ning Zhu, Chunlai Zeng
The natural medicinal monomer, schisandrin B (Sch B), has been shown to exert cardioprotective effects; however, the underlying mechanisms of these effects remain to be fully elucidated. Therefore, the aim of the present study was to investigate whether Sch B attenuated myocardial ischemia/reperfusion (I/R) injury via the phosphoinositide 3‑kinases (PI3K)/Akt signaling pathway. To confirm this, I/R models were established in rats by ligation of the left anterior descending coronary artery. A group of animals were administered with Sch B (60 mg/kg, lavage) and/or the PI3K inhibitor, LY294002 (0...
October 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29115534/crosstalk-between-p38%C3%A2-mapk-and-caspase-9-regulates-mitochondria-mediated-apoptosis-induced-by-tetra-%C3%AE-4-carboxyphenoxy-phthalocyanine-zinc-photodynamic-therapy-in-lovo-cells
#17
Yu Wang, Chunhui Xia, Zhiqiang Lun, Yanxin Lv, Wei Chen, Tao Li
Photodynamic therapy (PDT) is considered to be an advancing antitumor technology. PDT using hydrophilic/lipophilic tetra‑α-(4-carboxyphenoxy) phthalocyanine zinc (TαPcZn-PDT) has exhibited antitumor activity in Bel-7402 hepatocellular cancer cells. However, the manner in which p38 MAPK and caspase-9 are involved in the regulation of mitochondria-mediated apoptosis in the TαPcZn-PDT-treated LoVo human colon carcinoma cells remains unclear. Therefore, in the present study, a siRNA targeting p38 MAPK (siRNA-p38 MAPK) and the caspase‑9 specific inhibitor z-LEHD-fmk were used to examine the crosstalk between p38 MAPK and caspase-9 during mitochondria-mediated apoptosis in the TαPcZn-PDT‑treated LoVo cells...
November 2, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29115508/dj%C3%A2-1-alleviates-high-glucose%C3%A2-induced-endothelial-cells-injury-via-pi3k-akt%C3%A2-enos-signaling-pathway
#18
Hongan Tian, Shunzhen Li, Kaihu Yu
Hyperglycemia mediated endothelial cells (ECs) injury is closely associated with diabetic vascular complications. It was revealed that DJ‑1 possesses cellular protective effects by suppressing oxidative stress. The present study aimed to investigate the beneficial effects of DJ‑1 on high glucose (HG)‑induced human umbilical vein endothelial cell (HUVEC) injury and to elucidate its underlying mechanisms. HUVECs were incubated under 5.5 mM (control group) or 25 mM D‑glucose (HG group) and then transfected with recombinant adenoviral vectors to overexpression of DJ‑1...
November 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29115459/isolariciresinol-9-o-%C3%AE-l-arabinofuranoside-protects-against-hydrogen-peroxide%C3%A2-induced-apoptosis-of-human-umbilical-vein-endothelial-cells-via-a-pi3k-akt-bad%C3%A2-dependent-pathway
#19
Li-Tao Liu, Lei Liang, Wei Wang, Cui-Qi Yan, Jing Zhang, Yun-Chuan Xiao, Liang Ye, Man-Xi Zhao, Quan-Shu Huang, Jun-Jie Bian, Zhang-Fei Shi, Xiao Ke, Zhi-Rong Zhang
Isolariciresinol-9'-O-α-L-arabinofuranoside (MWS‑19) isolated from Pinus massoniana Lamb. Fresh pine needles is the major ingredient of the Songling Xuemaikang capsule therapy used for hypertension. The present study aimed to investigate the effects and underlying mechanisms of MWS‑19 on hydrogen peroxide (H2O2)‑induced apoptosis in human umbilical vein endothelial cells (HUVECs). To investigate the effect of MWS‑19 on apoptosis in HUVECs, an oxidative stress‑induced apoptosis model was established in HUVECs using H2O2, and the present study performed Hoechst 33258 staining and a Cell Counting Kit‑8 (CCK‑8) assay...
October 25, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29115406/berberine-prevents-the-apoptosis-of-mouse-podocytes-induced-by-traf5-overexpression-by-suppressing-nf-%C3%AE%C2%BAb-activation
#20
Feng Wu, Dong-Sheng Yao, Tian-Ying Lan, Chen Wang, Jian-Dong Gao, Li-Qun He, Di Huang
Berberine (BBR) has previously been found to exert beneficial effects on renal injury in experimental rats. However, the mechanisms underlying these effects are not yet fully understood. Tumor necrosis factor (TNF) receptor-associated factor 5 (TRAF5) has been demonstrated to mediate the activation of nuclear factor-κB (NF-κB), which has been implicated in the pathogenesis of chronic kidney disease (CKD). The aim of this study was to investigate the effects of BBR on kidney injury and the activation of the NF-κB signaling pathway in mouse podocytes...
November 7, 2017: International Journal of Molecular Medicine
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