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Bcl-2 protein inhibitors

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https://www.readbyqxmd.com/read/29156797/jq1-synergizes-with-the-bcl-2-inhibitor-abt-263-against-mycn-amplified-small-cell-lung-cancer
#1
Huogang Wang, Bo Hong, Xuemin Li, Ke Deng, Hong Li, Vivian Wai Yan Lui, Wenchu Lin
Small cell lung cancer (SCLC) is a clinically aggressive cancer with very poor prognosis. Amplification of MYC family genes and overexpression of Bcl-2 protein are common in SCLC, and they are likely therapeutic targets for SCLC. Previous clinical study showed that single agent targeting Bcl-2 with ABT-263 was of limited efficacy in SCLC. In this study, we demonstrated for the first time that co-targeting of N-Myc and Bcl-2 resulted in marked synergistic antitumor effects in MYCN-amplified SCLC. We found that MYCN-amplified SCLC cells were highly sensitive to a Bromodomain and Extra-Terminal domain (BET) inhibitor JQ1, which was able to inhibit N-Myc protein expression...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29154466/%C3%AE-fosb-regulates-rosiglitazone-induced-milk-fat-synthesis-and-cell-survival
#2
Xuefeng Wei, Hui Li, Guangwei Zhao, Jiameng Yang, Lihui Li, Yongzhen Huang, Xianyong Lan, Yun Ma, Huiling Zheng, Hong Chen
Rosiglitazone induces adipogenesis in adipocyte and regulates cell survival and differentiation in number of cell types. However, whether PPARγ regulates the synthesis of milk fat and cell survival in goat mammary gland remains unknown. Rosiglitazone strongly enhanced cellular triacylglycerol content and accumulation of lipid droplet in goat mammary epithelial cells (GMEC). Furthermore, ΔFosB decreased the expression of PPARγ at both mRNA and protein levels, and rosiglitazone-induced milk fat synthesis was abolished by ΔFosB overexpression...
November 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29151915/phloretin-induces-apoptosis-of-human-esophageal-cancer-via-a-mitochondria-dependent-pathway
#3
Hongtao Duan, Ruixuan Wang, Xiaolong Yan, Honggang Liu, Yong Zhang, Deguang Mu, Jing Han, Xiaofei Li
2,4,6-trihydroxy-3-(4-hydroxyphenyl)-propiophenone (phloretin) is found in apple tree leaves and the Manchurian apricot, and is a potent compound that exhibits anti-inflammatory, antioxidant and antitumor activities. However, the effect of phloretin on esophageal cancer cells is not well-defined. The present study aimed to examine whether and how phloretin induced apoptosis in human esophageal cancer cells. EC-109 cells were cultured in Dulbecco's modified Eagle's medium and incubated with 60, 70, 80, 90 and 100 µg/ml phloretin for 6, 12, 24 and 48 h...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29151909/bkm120-sensitizes-c6-glioma-cells-to-temozolomide-via-suppression-of-the-pi3k-akt-nf-%C3%AE%C2%BAb-mgmt-signaling-pathway
#4
Mao Li, Ruo Fei Liang, Xiang Wang, Qing Mao, Yan Hui Liu
Glioblastoma is the most common type of malignant intracranial tumor in adults. Temozolomide (TMZ), as the first-line chemotherapy agent used in patients with glioblastoma, has demonstrated different effects in patients due to the expression of O6-methylguanine-DNA methyltransferase (MGMT) which is able to repair the DNA lesions induced by TMZ. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway is over-activated in glioblastoma and has been revealed to be potentially implicated in resistance to TMZ...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29149414/role-of-tctp-for-cellular-differentiation-and-cancer-therapy
#5
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
#6
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
#7
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
#8
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
#9
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/29137527/binding-modes-of-bcl-2-homology-3-bh3-peptides-with-anti-apoptotic-protein-a1-and-redesign-of-peptide-inhibitors-a-computational-study
#10
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/29132010/inhibition-of-sonic-hedgehog-signaling-blocks-cell-migration-and-growth-but-induces-apoptosis-via-suppression-of-foxq1-in-natural-killer-t-cell-lymphoma
#11
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/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/29115607/schisandrin-b-protects-against-myocardial-ischemia-reperfusion-injury-via-the-pi3k-akt-pathway-in-rats
#13
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/29115508/dj%C3%A2-1-alleviates-high-glucose%C3%A2-induced-endothelial-cells-injury-via-pi3k-akt%C3%A2-enos-signaling-pathway
#14
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
#15
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/29115375/persistent-stat5-mediated-ros-production-and-involvement-of-aberrant-p53-apoptotic-signaling-in-the-resistance-of-chronic-myeloid-leukemia-to-imatinib
#16
Yanhong Cheng, Yingchan Hao, Aimei Zhang, Chaojie Hu, Xiaoxiao Jiang, Quan Wu, Xiucai Xu
The persistent activation of signal transducer and activator of transcription 5 (STAT5) may principally be attributed to breakpoint cluster region (BCR)-Abelson murine leukemia viral oncogene homolog 1 (ABL1), and have multi-faceted effects in the development of chronic myeloid leukemia (CML). The p53 protein network regulates important mechanisms in DNA damage repair, cell cycle regulation/checkpoints, and cell senescence and apoptosis, as demonstrated by its ability to positively regulate the expression of various pro-apoptotic genes, including B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax)...
October 20, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29113283/epigallocatechin-3-gallate-induces-apoptosis-in-acute-promyelocytic-leukemia-cells-via-a-shp-1-p38%C3%AE-mapk-bax-cascade
#17
Liugen Gan, Liang Zhong, Zhiling Shan, Chunlan Xiao, Ting Xu, Hao Song, Liu Li, Rong Yang, Beizhong Liu
Acute promyelocytic leukemia (APL) is characterized by a specific chromosomal translation, resulting in a fusion gene that affects the differentiation, proliferation and apoptosis of APL cells. Epigallocatechin-3-gallate (EGCG), a catechin, exhibits numerous biological functions, including antitumor activities. Previous studies have reported that EGCG induces apoptosis in NB4 cells. However, the molecular mechanism underlying EGCG-induced apoptosis remains unclear. The present study aimed to determine the molecular basis of EGCG-induced apoptosis in NB4 cells...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29113237/microrna-10a-suppresses-breast-cancer-progression-via-pi3k-akt-mtor-pathway
#18
Kongliang Ke, Tingting Lou
Previous studies have demonstrated that microRNA-10a (miR-10a) regulates various opposing biological functions in breast cancer. The aim of the present study was to investigate the exact functions of miR-10a in the pathogenesis of breast cancer. miR-10a expression was initially detected in two human breast cancer cell lines, MCF-7 and MDA-MB-231 and a normal human mammary epithelial cell line MCF-10A. The proliferation, migration and apoptosis of breast cancer cells were analyzed using MTT assays, Transwell assays and flow cytometry, respectively, following transfection of MCF-7 and MDA-MB-231 cells with an miR-10a mimic or anti-miR-10a...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29113186/puerarin-induces-cell-apoptosis-in-human-chondrosarcoma-cell-line-sw1353-via-inhibition-of-the-pi3k-akt-signaling-pathway
#19
Li Huang, Junqing Cao, Lan Cao, Ling Gao, Ying Yang, Li Xu
Chondrosarcoma is a malignant soft tissue sarcoma with poor prognosis. Puerarin has been demonstrated to possess anticancer properties; however, the effects of puerarin in human chondrosarcoma cells remain unknown. The present study aimed to investigate the anticancer effects of puerarin in SW1353 human chondrosarcoma cells. SW1353 cells were treated with increasing concentrations of puerarin for different durations. Cell viability was evaluated using MTT assays. Cell apoptosis rates were determined by flow cytometry...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29111964/a-phylogenetic-and-evolutionary-analysis-of-antimycin-biosynthesis
#20
Rebecca Joynt, Ryan F Seipke
Streptomyces species and other Actinobacteria are ubiquitous in diverse environments worldwide and are the source of, or inspiration for, the majority of antibiotics. The genomic era has enhanced biosynthetic understanding of these valuable chemical entities and has also provided a window into the diversity and distribution of natural product biosynthetic gene clusters. Antimycin is an inhibitor of mitochondrial cytochrome c reductase and more recently was shown to inhibit Bcl-2/Bcl-XL-related anti-apoptotic proteins commonly overproduced by cancerous cells...
November 7, 2017: Microbiology
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