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Bcl-2 family proteins

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https://www.readbyqxmd.com/read/29331753/an-iridium-iii-complex-as-potent-anticancer-agent-induces-apoptosis-and-autophagy-in-b16%C3%A2-cells-through-inhibition-of-the-akt-mtor-pathway
#1
Bing Tang, Dan Wan, Yang-Jie Wang, Qiao-Yan Yi, Bo-Hong Guo, Yun-Jun Liu
A new ligand THPDP (THPDP = 11-(6,7,8,9-tetrahydrophenazin-2-yl)dipyrido[3,2-a:2',3'-c]phenazine) and its iridium(III) complex [Ir(ppy)2(THPDP)]PF6 (Ir-1) was synthesized and characterized by elemental analysis, IR, ESI-MS, 1H NMR and 13C NMR. The cytotoxicity in vitro of the complex against cancer cells B16, A549, Eca-109, SGC-7901, BEL-7402 and normal NIH 3T3 cell lines was evaluated using MTT method. The IC50 values of the complex toward B16, A549 and Eca-109 cells are 1.0 ± 0.02, 1.4 ± 0...
December 30, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29323899/optimization-of-potent-and-selective-tricyclic-indole-diazepinone-myeloid-cell-leukemia-1-mcl-1-inhibitors-using-structure-based-design
#2
Subrata Shaw, Zhiguo Bian, Bin Zhao, James C Tarr, Nagarathanam Veerasamy, KyuOk Jeon, Johannes Belmar, Allison L Arnold, Stuart A Fogarty, Evan Perry, John L Sensintaffar, DeMarco V Camper, Olivia W Rossanese, Taekyu Lee, Edward T Olejniczak, Stephen W Fesik
Myeloid cell leukemia 1 (Mcl-1), an anti-apoptotic member of the Bcl-2 family of proteins, has emerged as an attractive target for cancer therapy. Mcl-1 upregulation is often found in many human cancers and is associated with high tumor grade, poor survival, and resistance to chemotherapy. Here we describe a series of potent and selective tricyclic indole diazepinone Mcl-1 inhibitors that were discovered and further optimized using structure-based design. These compounds exhibit picomolar binding affinity and mechanism-based cellular efficacy, including growth inhibition and caspase induction in Mcl-1 sensitive cells...
January 11, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29318910/cloning-of-a-novel-lectin-from-artocarpus-lingnanensis-that-induces-apoptosis-in-human-b-lymphoma-cells
#3
Yu Luo, Xiaoqin Liu, Faquan Lin, Liejun Liao, Yong Deng, Linjie Zeng, Qiyan Zeng
We isolated a novel lectin (Artocarpus nitidus subsp. lingnanensis lectin, ALL) from Artocarpus nitidus subsp. lingnanensis and showed its mitogenic activities. In this study, we determined the amino acid sequence of ALL by cDNA sequencing. ALL cDNA (933 bp) contains a 657-bp open reading frame (ORF), which encodes a protein with 218 amino acids. ALL shares high sequence similarities with Jacalin and Morniga G and belongs to jacalin-related lectin family. We also examined the antitumor activity of ALL using Raji, a human B-lymphoma cell line...
January 10, 2018: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/29316737/the-effect-of-lipopolysaccharide-on-noxa-expression-is-mediated-through-irf-1-3-and-7
#4
Sujan Piya, Tae-Hyoung Kim
Lipopolysaccharide (LPS), a component of the cell wall of gram-negative bacteria, elicits the secretion of cytokines, such as interferons, that stimulate the host defense system. Previously, we demonstrated that interferons induce interferon regulatory factors (IRFs) 1, 3, and 7 that regulate transcription of Noxa and alter expression profiles of Bcl-2 family proteins in tumors. However, the immediate consequences of LPS stimulation on Noxa and BH3 expression in tumor cells remain uncharacterized. Here, we determined that LPS induced Noxa expression in CT26 cells...
January 11, 2018: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29312623/notoginsenoside-r7-suppresses-cervical-cancer-via-pi3k-pten-akt-mtor-signaling
#5
Li Li, Jin-Xia Sun, Xiao-Qi Wang, Xiao-Kai Liu, Xian-Xiong Chen, Bo Zhang, Zhen-Dan He, Dong-Zhou Liu, Li-Xin Chen, Li-Wei Wang, Zhong Huang
Notoginsenoside R7 was isolated from Panax notoginseng, a plant used commonly in traditional Chinese medicine. We investigated the anti-cancer effects of R7 in HeLa cells in vitro and in vivo, and explored the underlying mechanisms of action. R7 dose-dependently inhibited HeLa cell proliferation and induced apoptosis in vitro, In silico docking-based screening assays showed that R7 can directly bind Akt. Pretreatment with the Akt inhibitor LY294002 synergistically enhanced the R7 anti-proliferation and anti-apoptosis effects in HeLa cells, confirming that R7 acts through the PI3K/Akt pathway...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29312593/shikonin-induces-ros-based-mitochondria-mediated-apoptosis-in-colon-cancer
#6
Wenquan Liang, Jianxin Cui, Kecheng Zhang, Hongqing Xi, Aizhen Cai, Jiyang Li, Yunhe Gao, Chong Hu, Yi Liu, Yixun Lu, Ning Wang, Xiaosong Wu, Bo Wei, Lin Chen
Colon cancer is the third most common malignancy worldwide, and chemotherapy is a widely used strategy in clinical therapy. Chemotherapy-resistant of colon cancer is the main cause of recurrence and progression. Novel drugs with efficacy and safety in treating colon cancer are urgently needed. Shikonin, a naphthoquinone derived from the roots of the herbal plant Lithospermum erythrorhizon, has been determined to be a potent anti-tumor agent. The aim of the present study was to detect the underlying anti-tumor mechanism of shikonin in colon cancer...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29304561/crosstalk-between-cellular-redox-state-and-the-anti-apoptotic-protein-bcl-2
#7
Sebastian Other-Gee Pohl, Mark Agostino, Arun Dharmarajan, Shazib Pervaiz
SIGNIFICANCE B cell lymphoma-2 (Bcl-2) is the prototypical anti-apoptotic member of the Bcl-2 family that comprises proteins with contrasting effects on cell fate. Identified as a consequence chromosomal translocation (t 14:18) in human lymphoma, subsequent studies have revealed mutations and/or copy number alterations, as well as post-translational modifications, of Bcl-2 in a variety of cancers. The canonical function of Bcl-2 is linked to its ability to inhibit mitochondrial membrane permeabilization, regulating apoptosome assembly and activation by blocking cytosolic translocation of death amplification factors...
January 5, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29298131/a-systematic-review-of-p53-regulation-of-oxidative-stress-in-skeletal-muscle
#8
Kaitlyn Beyfuss, David A Hood
BACKGROUND: p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis. METHODS: A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases...
January 3, 2018: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/29296199/costunolide-enhances-doxorubicin-induced-apoptosis-in-prostate-cancer-cells-via-activated-mitogen-activated-protein-kinases-and-generation-of-reactive-oxygen-species
#9
Jiasheng Chen, Binshen Chen, Zhihui Zou, Wei Li, Yiming Zhang, Jinlin Xie, Chunxiao Liu
The management of castration-resistant prostate cancer (CRPC) is challenging, attributable to a lack of efficacious therapies. Chemotherapy is one of the most important treatments for CRPC. Doxorubicin has been extensively used in many different tumors and is often combined with other drugs to enhance effects and reduce toxicity. Costunolide is a natural sesquiterpene lactone with anti-cancer properties. In this study, we first demonstrated that the combination of costunolide and doxorubicin induced apoptosis significantly more than either drug alone in prostate cancer cell lines...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29291023/combined-venetoclax-and-alvocidib-in-acute-myeloid-leukemia
#10
James Bogenberger, Clifford Whatcott, Nanna Hansen, Devora Delman, Chang-Xin Shi, Wontak Kim, Hillary Haws, Katherine Soh, Ye Sol Lee, Peter Peterson, Adam Siddiqui-Jain, Steven Weitman, Keith Stewart, David Bearss, Ruben Mesa, Steven Warner, Raoul Tibes
More effective treatment options for elderly acute myeloid leukemia (AML) patients are needed as only 25-50% of patients respond to standard-of-care therapies, response duration is typically short, and disease progression is inevitable even with some novel therapies and ongoing clinical trials. Anti-apoptotic BCL-2 family inhibitors, such as venetoclax, are promising therapies for AML. Nonetheless, resistance is emerging. We demonstrate that venetoclax combined with cyclin-dependent kinase (CDK) inhibitor alvocidib is potently synergistic in venetoclax-sensitive and -resistant AML models in vitro, ex vivo and in vivo...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29287955/remodeling-of-ca2-signaling-in-cancer-regulation-of-inositol-1-4-5-trisphosphate-receptors-through-oncogenes-and-tumor-suppressors
#11
REVIEW
Hideaki Ando, Katsuhiro Kawaai, Benjamin Bonneau, Katsuhiko Mikoshiba
The calcium ion (Ca2+) is a ubiquitous intracellular signaling molecule that regulates diverse physiological and pathological processes, including cancer. Increasing evidence indicates that oncogenes and tumor suppressors regulate the Ca2+ transport systems. Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are IP3-activated Ca2+ release channels located on the endoplasmic reticulum (ER). They play pivotal roles in the regulation of cell death and survival by controlling Ca2+ transfer from the ER to mitochondria through mitochondria-associated ER membranes (MAMs)...
December 20, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29287727/upregulation-of-mcl-1-inhibits-jq1-triggered-anticancer-activity-in-hepatocellular-carcinoma-cells
#12
Hua-Peng Zhang, Gong-Quan Li, Yi Zhang, Wen-Zhi Guo, Jia-Kai Zhang, Jie Li, Jian-Feng Lv, Shui-Jun Zhang
Bromodomains and extra-terminal (BET) proteins inhibitors are promising cancer therapeutic agents. However, tumor cells often develop resistance to BET inhibitors, greatly limiting their therapeutic potential. To study the mechanism underlying the resistance of BET inhibitors in hepatocellular carcinoma (HCC) cells, we herein investigated the impact of BET inhibitor JQ1 on the gene expression of Bcl-2 family members by RNA sequencing analysis, and found that acute treatment with JQ1 triggered upregulation of Mcl-1 in HCCLM3 and BEL7402 cell lines...
December 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29285195/14-3-3%C3%AE%C2%B5-is-a-nuclear-matrix-protein-and-its-altered-expression-and-localization-are-associated-with-curcumin-induced-apoptosis-of-mg-63-cells
#13
Kun Lu, Gang Rui, Fan Liu, Ling Yang, Xiaoling Deng, Songlin Shi, Qifu Li
The 14-3-3 protein family may regulates protein interaction, transportation and cellular localization. The regulatory role of 14-3-3ε is influenced by its altered localization. In the present study, human osteosarcoma MG-63 cells were treated with curcumin to induce apoptosis. Subsequently, the altered expression and localization of 14-3-3ε and its co-localization with other apoptosis-associated proteins during apoptosis was investigated. Analysis of nuclear matrix proteins (NMPs), using two-dimensional gel electrophoresis with matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry, revealed that 14-3-3ε existed on the nuclear matrix of MG-63 cells, and its expression was decreased compared with that in control cells following curcumin treatment...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29278807/myricetin-enhances-on-apoptosis-induced-by-serum-deprivation-in-pc12-cells-mediated-by-mitochondrial-signaling-pathway
#14
Gongxun Tan, Rachael A Uson-Lopez, Md Mostafizur Rahman, Toshiyuki Hosokawa, Takeshi Saito, Masaaki Kurasaki
Polyphenols have many beneficial effects and an effective disease therapeutic auxiliary drug. Previously, myricetin, a polyphenol, had been reported to possess various biological effects on human physiology. However, mechanism of myricetin on apoptosis induced in PC12 cells is still unclear. PC12 cells were treated with myricetin in two concentration levels comprising 0.1 and 1 μM under serum-free condition. As a result, morphological changes were observed using trypan blue assay. DNA fragmentation was determined by DNA ladder assay to evaluate DNA damage levels...
December 18, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29278499/bim-binding-remotely-regulates-bax-activation-insights-from-the-free-energy-landscapes
#15
Souvik Sinha, Atanu Maity, Shubhra Ghosh Dastidar
Activation of the pro-apoptotic BAX protein, a BCl-2 family member, is known to trigger the apoptosis by forming pores in the mitochondrial outer membrane (MOM). While in the cytosol, release of its transmembrane C-terminal helix (called α9 helix) from a well-characterized binding pocket (BC groove) and subsequent permeabilization of MOM is understood to be the initiating events of the activation. In concern of what initiates the BAX activation, so far one plausible suggestion has been that the transient attachment of BH3-only peptide on a distal site from BC groove triggers the activation process...
December 26, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29276033/crystal-structures-of-anti-apoptotic-bfl-1-and-its-complex-with-a-covalent-stapled-peptide-inhibitor
#16
Edward P Harvey, Hyuk-Soo Seo, Rachel M Guerra, Gregory H Bird, Sirano Dhe-Paganon, Loren D Walensky
BCL-2 family proteins are high-priority cancer targets whose structures provide essential blueprints for drug design. Whereas numerous structures of anti-apoptotic BCL-2 protein complexes with α-helical BH3 peptides have been reported, the corresponding panel of apo structures remains incomplete. Here, we report the crystal structure of apo BFL-1 at 1.69-Å resolution, revealing similarities and key differences among unliganded anti-apoptotic proteins. Unlike all other BCL-2 proteins, apo BFL-1 contains a surface-accessible cysteine within its BH3-binding groove, allowing for selective covalent targeting by a NOXA BH3-based stapled peptide inhibitor...
December 6, 2017: Structure
https://www.readbyqxmd.com/read/29259001/apoptosis-in-megakaryocytes-and-platelets-life-and-death-of-a-lineage
#17
Kate McArthur, Stephane Chappaz, Benjamin T Kile
Despite their profoundly different cellular composition, size and function, megakaryocytes and platelets both depend on restraint of the intrinsic (or "mitochondrial") apoptosis pathway by BCL-2 family pro-survival proteins for their development and viability. Activation of the pathway contributes to the clearance of megakaryocytes following platelet shedding, and constrains platelet life span in the circulation. Important questions remain as to how apoptosis is initiated in these cells at steady state and in response to pathophysiological insults...
December 19, 2017: Blood
https://www.readbyqxmd.com/read/29250183/ampelopsin-induced-reactive-oxygen-species-enhance-the-apoptosis-of-colon-cancer-cells-by-activating-endoplasmic-reticulum-stress-mediated-ampk-mapk-xaf1-signaling
#18
Ga Bin Park, Jee-Yeong Jeong, Daejin Kim
Ampelopsin (Amp) is bioactive natural product and exerts anti-cancer effects against several cancer types. The present study investigated the anti-colon cancer activity of Amp and explored its mechanism of action. The treatment of colon cancer cells with Amp resulted in the dose- and time-dependent induction of apoptosis via the activation of endoplasmic reticulum (ER) stress, 5' adenosine monophosphate-activated protein kinase (AMPK), and c-Jun N-terminal protein kinase (JNK)/p38 mitogen-activated protein kinases (MAPKs)...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29243082/dihydroquercetin-ameliorated-acetaminophen-induced-hepatic-cytotoxicity-via-activating-jak2-stat3-pathway-and-autophagy
#19
Wenjing Zai, Wei Chen, Jingyun Luan, Jiajun Fan, Xuyao Zhang, Zimei Wu, Tao Ding, Dianwen Ju, Hongrui Liu
Acetaminophen (APAP) overdose is currently the leading cause of acute liver disease, but therapeutic treatment strategies are commonly limited. Although dihydroquercetin (DHQ) is an attractive botanical antioxidant, its protective potential for liver disease remains elusive. The present study investigated the protective effects of DHQ against APAP-induced hepatic cytotoxicity. Primary mouse hepatocytes were treated with different concentrations of DHQ followed by APAP administration. Our data showed that DHQ relieved APAP-induced growth inhibition and lactate dehydrogenase (LDH) release in a dose-dependent manner, as well as inhibited APAP-induced necrosis and extracellular signal regulated kinase-c-Jun-N-terminal kinase (ERK-JNK) stress...
December 14, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29229991/bok-promotes-chemical-induced-hepatocarcinogenesis-in-mice
#20
Tatiana Rabachini, Yuniel Fernandez-Marrero, Matteo Montani, Giulio Loforese, Valentina Sladky, Zhaoyue He, Daniel Bachmann, Simone Wicki, Andreas Villunger, Deborah Stroka, Thomas Kaufmann
BCL-2-related ovarian killer (BOK) is a conserved and widely expressed BCL-2 family member with sequence homology to pro-apoptotic BAX and BAK, but with poorly understood pathophysiological function. Since several members of the BCL-2 family are critically involved in the regulation of hepatocellular apoptosis and carcinogenesis we aimed to establish whether loss of BOK affects diethylnitrosamine (DEN)-induced hepatocarcinogenesis in mice. Short-term exposure to DEN lead to upregulation of BOK mRNA and protein in the liver...
December 11, 2017: Cell Death and Differentiation
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