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Bcl-2 family proteins

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https://www.readbyqxmd.com/read/28529715/inducing-death-in-tumor-cells-roles-of-the-inhibitor-of-apoptosis-proteins
#1
REVIEW
Darren Finlay, Peter Teriete, Mitchell Vamos, Nicholas D P Cosford, Kristiina Vuori
The heterogeneous group of diseases collectively termed cancer results not just from aberrant cellular proliferation but also from a lack of accompanying homeostatic cell death. Indeed, cancer cells regularly acquire resistance to programmed cell death, or apoptosis, which not only supports cancer progression but also leads to resistance to therapeutic agents. Thus, various approaches have been undertaken in order to induce apoptosis in tumor cells for therapeutic purposes. Here, we will focus our discussion on agents that directly affect the apoptotic machinery itself rather than on drugs that induce apoptosis in tumor cells indirectly, such as by DNA damage or kinase dependency inhibition...
2017: F1000Research
https://www.readbyqxmd.com/read/28529565/prodelphinidins-isolated-from-chinese-bayberry-leaves-induces-apoptosis-via-the-p53-dependent-signaling-pathways-in-ovcar-3-human-ovarian-cancer-cells
#2
Yu Fu, Xingqian Ye, Malcolm Lee, Gary Rankin, Yi Charlie Chen
Chinese bayberry leaves are rich in prodelphinidins. Since the isolation and purification of prodelphinidins is difficult, the association between the degree of prodelphinidin polymerization and their anti-carcinogenic activity remains ambiguous. The cytotoxic and apoptotic activities of prodelphinidin Chinese bayberry leaf extracts (PCBLs), oligomeric proanthocyanidins (OPAs) and polymeric proanthocyanidins (PPAs), isolated by normal-phase preparative high-performance liquid chromatography were investigated in OVCAR-3 human ovarian cancer cells...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28528322/very-low-doses-of-heavy-oxygen-ion-radiation-induce-premature-ovarian-failure
#3
Birendra Mishra, Ryan Ripperdan, Laura Ortiz, Ulrike Luderer
Astronauts are exposed to charged particles during space travel, and charged particles are also used for cancer radiotherapy. Premature ovarian failure is a well-known side-effect of conventional, low linear energy transfer (LET) cancer radiotherapy, but little is known about the effects of high LET charged particles on the ovary. We hypothesized that lower LET (16.5 keV/µm) oxygen particles would be less damaging to the ovary than we previously found for iron (LET=179 keV/µm). Adult female mice were irradiated with 0, 5, 30, or 50 cGy oxygen ions or 50 cGy oxygen plus dietary supplementation with the antioxidant alpha lipoic acid (ALA)...
May 20, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28522750/inhibition-of-mitochondrial-matrix-chaperones-and-anti-apoptotic-bcl-2-family-proteins-empower-antitumor-therapeutic-responses
#4
Georg Karpel-Massler, Chiaki Tsuge Ishida, Elena Bianchetti, Chang Shu, Rolando Perez-Lorenzo, Basil Horst, Matei Banu, Kevin A Roth, Jeffrey N Bruce, Peter Canoll, Dario C Altieri, Markus D Siegelin
Rational therapeutic approaches based on synthetic lethality may improve cancer management. Based on a high-throughput drug screen, we provide preclinical proof of concept that targeting the mitochondrial Hsp90 chaperone network (mtHsp90) and inhibition of Bcl-2, Bcl-xL and Mcl-1 is sufficient to elicit synthetic lethality in tumors recalcitrant to therapy. Our analyses focused on BH3 mimetics that are broad acting (ABT263 and Obatoclax) or selective (ABT199, WEHI-539 and A1210477), along with the established mitochondrial matrix chaperone inhibitor Gamitrinib-TPP...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28516063/modulation-of-ca-2-signaling-by-anti-apoptotic-b-cell-lymphoma-2-proteins-at-the-endoplasmic-reticulum-mitochondrial-interface
#5
REVIEW
Tim Vervliet, Eva Clerix, Bruno Seitaj, Hristina Ivanova, Giovanni Monaco, Geert Bultynck
Mitochondria are important regulators of cell death and cell survival. Mitochondrial Ca(2+) levels are critically involved in both of these processes. On the one hand, excessive mitochondrial Ca(2+) leads to Ca(2+)-induced mitochondrial outer membrane permeabilization and thus apoptosis. On the other hand, mitochondria need Ca(2+) in order to efficiently fuel the tricarboxylic acid cycle and maintain adequate mitochondrial bioenergetics. For obtaining this Ca(2+), the mitochondria are largely dependent on close contact sites with the endoplasmic reticulum (ER), the so-called mitochondria-associated ER membranes...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28511583/deciphering-the-crucial-residues-involved-in-heterodimerization-of-bak-peptide-and-anti-apoptotic-proteins-for-apoptosis
#6
Parthiban Marimuthu, Kalaimathy Singaravelu
B-cell lymphoma 2 (Bcl-2) family proteins are the central regulators of apoptosis, function via mitochondrial outer membrane permeabilization. The family members are involved in several stages of apoptosis regulation. The overexpression of the anti-apoptotic proteins leads to several cancer pathological conditions. This overexpression is modulated or inhibited by heterodimerization of pro-apoptotic BH3 domain or BH3-only peptides to the hydrophobic groove present at the surface of anti-apoptotic proteins. Additionally, the heterodimerization displayed differences in binding affinity profile among the pro-apoptotic peptides binding to anti-apoptotic proteins...
May 16, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28493377/neonatal-myeloid-derived-suppressor-cells-show-reduced-apoptosis-and-immunosuppressive-activity-upon-infection-with-escherichia-coli
#7
Anja Leiber, Julian Schwarz, Natascha Köstlin, Bärbel Spring, Birgit Fehrenbach, Nenad Katava, Christian F Poets, Christian Gille
BACKGROUND: Susceptibility to infection during the neonatal period and reduced control of inflammation in neonates are attributed to immunosuppression persisting from fetal life. Myeloid-derived suppressor cells (MDSCs) are immature myeloid progenitors with suppressive activity and increased numbers in cord blood. We hypothesized that MDSCs contribute to innate host defence in neonates, paralleled by anti-inflammatory signalling. METHODS: Phagocytic activity, infection induced apoptosis, expression of B-cell lymphoma (Bcl)-2 family proteins, production of reactive oxygen species (ROS), cytokine production and T-cell suppression of neonatal granulocytic-MDSCs (G-MDSCs) after infection with Escherichia coli (E...
May 11, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28488118/isoliquiritigenin-induces-cytotoxicity-in-pc-12-cells-in-vitro
#8
Hui-Hui Yang, Cheng Zhang, Shang-Hai Lai, Chuan-Chuan Zeng, Yun-Jun Liu, Xiu-Zhen Wang
Isoliquiritigenin (ISL) has been reported to have a wide range of biological activities. This study evaluated the cytotoxic effect of ISL on norvegicus pheochromocytoma cell line (PC-12 cells) and its possible molecular mechanism. The cytotoxicity in vitro of ISL against PC-12 cells was investigated by MTT assay. The migration and invasion of PC-12 cells were performed by scratch test and transwell assay. Apoptosis was evaluated by microscopy and flow cytometry. The reactive oxygen species (ROS) and mitochondrial membrane potential were studied by fluorescent microscopy...
May 9, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28486557/downregulation-of-anp32b-exerts-anti-apoptotic-effects-in-hepatocellular-carcinoma
#9
Yoshinori Ohno, Mitsuhito Koizumi, Hironao Nakayama, Takao Watanabe, Masashi Hirooka, Yoshio Tokumoto, Taira Kuroda, Masanori Abe, Shinji Fukuda, Shigeki Higashiyama, Teru Kumagi, Yoichi Hiasa
The acidic (leucine-rich) nuclear phosphoprotein 32 family member B (ANP32B), a highly conserved member of the acidic nuclear phosphoprotein 32 (ANP32) family, is critical for the development of normal tissue. However, its role in the development of hepatocellular carcinoma (HCC) is controversial. In this study, we elucidated the role of ANP32B in HCC cell lines and tissues. ANP32B expression in HCC cell lines was modulated using siRNA and ANP32B expression plasmids and lentiviruses. The levels of apoptosis-related proteins were analyzed by real-time RT-PCR and Western blotting...
2017: PloS One
https://www.readbyqxmd.com/read/28477025/eribulin-alone-or-in-combination-with-the-plk1-inhibitor-bi-6727-triggers-intrinsic-apoptosis-in-ewing-sarcoma-cell-lines
#10
Lilly Magdalena Weiß, Manuela Hugle, Simone Fulda
In this study, we investigated the molecular mechanisms of eribulin-induced cell death and its therapeutic potential in combination with the PLK1 inhibitor BI 6727 in Ewing sarcoma (ES). Here, we show that eribulin triggers cell death in a dose-dependent manner in a panel of ES cell lines. In addition, eribulin at subtoxic, low nanomolar concentrations acts in concert with BI 6727 to induce cell death and to suppress long-term clonogenic survival. Mechanistic studies reveal that eribulin monotherapy at cytotoxic concentrations and co-treatment with eribulin at subtoxic concentrations together with BI 6727 arrest cells in the M phase of the cell cycle prior to the onset of cell death...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28472789/znf667-serves-as-a-putative-oncogene-in-human-hepatocellular-carcinoma
#11
Ke Cheng, Zhizhao Chen, Lian Liu, Yujun Zhao, Sheng Zhang, Qiang Wang, Zhenghao Deng, Sipin Tan, Qifa Ye
BACKGROUND/AIMS: Zinc finger protein 667 (ZNF667) is a member of C2H2 zinc finger protein family. For the first time, we aim to analyze the expression pattern of ZNF667 in hepatocellular carcinoma (HCC) tissues; to explore its role in HCC tumorigenesis. METHODS: Immuno-histochemistry was carried out to characterize the ZNF667 expression in paraffin-embedded HCC samples. The relationship between ZNF667 expression and the clinical, pathological data of the patients were analyzed...
May 4, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28472754/ruthenium-ii-polypyridyl-complexes-synthesis-characterization-and-anticancer-activity-studies-on-bel-7402-cells
#12
Dan Wan, Shang-Hai Lai, Chuan-Chuan Zeng, Cheng Zhang, Bing Tang, Yun-Jun Liu
Two new ligand PTTP (2-phenoxy-1,4,8,9-tetraazatriphenylene) and FTTP (2-(3-fluoronaphthalen-2-yloxy)-1,4,8,9-tetraazatriphenylene) and their six ruthenium(II) polypyridyl complexes [Ru(N-N)2(PTTP)](ClO4)2 and [Ru(N-N)2(FTTP)](ClO4)2 (N-N=dmb: 4,4'-dimethyl-2,2'-bipiridine; dmp: 2,9-dimethyl-1,10-phenanthroline; ttbpy: 4,4'-ditertiarybutyl-2,2'-bipyridine) were synthesized and characterized. The cytotoxic activity of the complexes against cancer cells HeLa, BEL-7402, A549, HepG-2, HOS and normal cell LO2 was evaluated by MTT method...
April 27, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28464919/the-role-of-apoptosis-repressor-with-a-card-domain-arc-in-the-therapeutic-resistance-of-renal-cell-carcinoma-rcc-the-crucial-role-of-arc-in-the-inhibition-of-extrinsic-and-intrinsic-apoptotic-signalling
#13
Csaba Toth, Sarah Funke, Vanessa Nitsche, Anna Liverts, Viktoriya Zlachevska, Marcia Gasis, Constanze Wiek, Helmut Hanenberg, Csaba Mahotka, Peter Schirmacher, Sebastian Heikaus
BACKGROUND: Renal cell carcinomas (RCCs) display broad resistance against conventional radio- and chemotherapies, which is due at least in part to impairments in both extrinsic and intrinsic apoptotic pathways. One important anti-apoptotic factor that is strongly overexpressed in RCCs and known to inhibit both apoptotic pathways is ARC (apoptosis repressor with a CARD domain). METHODS: Expression and subcellular distribution of ARC in RCC tissue samples and RCC cell lines were determined by immunohistochemistry and fluorescent immunohistochemistry, respectively...
May 2, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28462532/cell-death-and-thymic-tolerance
#14
REVIEW
Stephen R Daley, Charis Teh, Daniel Y Hu, Andreas Strasser, Daniel H D Gray
The differentiation of hematopoietic precursors into the many functionally distinct T-cell types produced by the thymus is a complex process. It proceeds through a series of stages orchestrated by a variety of thymic microenvironments that shape the T-cell developmental processes. Numerous cytokine and cell surface receptors direct thymocyte differentiation but the primary determinant of cell fate is the engagement of the T-cell antigen receptor (TCR). The strength of the TCR signal and the maturation stage of the thymocyte receiving it can direct the various differentiation programs or, alternatively, end the process by inducing cell death...
May 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28461171/connecting-mitochondrial-dynamics-and-life-or-death-events-via-bcl-2-family-proteins
#15
REVIEW
Abdel Aouacheria, Stephen Baghdiguian, Heather M Lamb, Jason D Huska, Fernando J Pineda, J Marie Hardwick
The morphology of a population of mitochondria is the result of several interacting dynamical phenomena, including fission, fusion, movement, elimination and biogenesis. Each of these phenomena is controlled by underlying molecular machinery, and when defective can cause disease. New understanding of the relationships between form and function of mitochondria in health and disease is beginning to be unraveled on several fronts. Studies in mammals and model organisms have revealed that mitochondrial morphology, dynamics and function appear to be subject to regulation by the same proteins that regulate apoptotic cell death...
April 28, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28456891/ccmp-and-cump-in-apoptosis-concepts-and-methods
#16
Sabine Wolter, Fanni Dittmar, Roland Seifert
The cyclic nucleotides cAMP and cGMP are well-characterized second messenger molecules regulating many important intracellular processes, such as differentiation, proliferation, and apoptosis. The latter is a highly regulated process of programmed cell death wherein several regulatory proteins, like those belonging to the Bcl-2 family, are involved. The initiation of apoptosis is regulated by three different pathways: the intrinsic or mitochondrial, the extrinsic, and the ER stress pathway. Recently, it has been published that the pyrimidine cyclic nucleotides cCMP and cUMP also function as second messenger molecules, and additionally have an effect on apoptosis signaling pathways...
2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28454339/puma-decreases-the-growth-of-prostate-cancer-pc-3-cells-independent-of-p53
#17
Zhengfei Shan, Qingzuo Liu, Yuling Li, Jitao Wu, Dekang Sun, Zhenli Gao
PUMA (p53 upregulated modulator of apoptosis), a member of the B-cell lymphoma 2 (Bcl-2) protein family, is a pro-apoptotic protein. PUMA expression is modulated by the tumor suppressor p53. PUMA has a role in rapid cell death via p53-dependent and -independent mechanisms. To evaluate whether p53 is required for PUMA-mediated apoptosis in prostate cancer cells, p53 protein was silenced in human prostate cancer PC-3 cells by using p53 small interfering RNA (siRNA). The interference efficiency of p53 on RNA and protein levels was detected by reverse transcription-quantitative polymerase chain reaction and western blotting...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28449207/targeting-anti-apoptotic-bcl2-family-proteins-in-haematological-malignancies-from-pathogenesis-to-treatment
#18
REVIEW
Meike Vogler, Harriet S Walter, Martin J S Dyer
The B-cell lymphoma 2 (BCL2) family of proteins comprise key regulators of apoptosis and are implicated in the pathogenesis of many malignancies, including lymphomas and leukaemias. Targeting of BCL2 proteins can be directly toxic to tumour cells or render them more sensitive to chemotherapy. Inhibition of the anti-apoptotic functions of BCL2 proteins using structure-based design to produce specific inhibitors of protein-protein interactions has been achieved for BCL2, MCL1 and BCL-XL (also termed BCL2L1), providing an armamentarium of new targeted therapies called BH3-mimetics...
April 27, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28447717/knockdown-of-zfpl1-results-in-increased-autophagy-and-autophagy%C3%A2-related-cell-death-in-nci%C3%A2-n87-and-bgc%C3%A2-823-human-gastric-carcinoma-cell-lines
#19
Yong-Zheng Xie, Wan-Li Ma, Ji-Ming Meng, Xue-Qun Ren
Macroautophagy, which will hereafter be referred to as autophagy, is an evolutionarily conserved process, during which cells recycle and remove damaged organelles and proteins in response to cellular stress. However, the mechanisms underlying the regulation of autophagy remain to be fully elucidated. The present study demonstrated that knockdown of zinc finger protein like 1 (ZFPL1) induces autophagy and increases autophagic cell death in NCI‑N87 and BGC‑823 human gastric carcinoma cell lines. To examine the role of ZFPL1 in gastric carcinoma cells, ZFPL1 expression was downregulated by lentiviral infection...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28447716/par1%C3%A2-mediated-c%C3%A2-jun-activation-promotes-heat-stress%C3%A2-induced-early-stage-apoptosis-of-human-umbilical-vein-endothelial-cells
#20
Shuang Zhang, Yanan Liu, Zhenglian Wang, Jingxian Liu, Zhengtao Gu, Qiulin Xu, Lei Su
Our previous study indicated that when human umbilical vein endothelial cells (HUVECs), which are involved in endothelial barrier function, are heat stressed, levels of protease‑activated receptor 1 (PAR1) are increased significantly. In the present study, it was demonstrated that PAR1 serves a vital role in heat stress‑induced HUVEC apoptosis. When the PAR1 inhibitor, SCH79797 (SCH), or a small interfering RNA (siRNA) targeting PAR1 were used to inhibit PAR1 signaling, a marked decrease in cell apoptosis, caspase‑3 activity and the expression of the pro‑apoptotic protein B‑cell lymphoma 2 (Bcl‑2) associated X (Bax), as well as increased expression of the anti‑apoptotic Bcl‑2 family member, myeloid cell leukemia 1 (Mcl‑1), were observed...
May 2017: Molecular Medicine Reports
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