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Bcl-2 protein inhibitors

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https://www.readbyqxmd.com/read/28330284/in-vitro-evaluation-of-anti-proliferative-anti-inflammatory-and-pro-apoptotic-activities-of-the-methanolic-extracts-of-andrographis-nallamalayana-ellis-on-a375-and-b16f10-melanoma-cell-lines
#1
Guroji Purushotham, Yerukala Padma, Yusuf Nabiha, R R Venkata Raju
Natural plant products have been widely used in controlling cancer with fewer or no side effects and the use of plant extracts as complementary to synthetic medicine is gaining increased popularity. Members of Andrographis plants possess important medicinal properties. In the present study, anti-cancerous properties of Andrographis nallamalayana (AN) were tested on A375 and B16F10 skin melanoma cancer cell lines. The leaf extracts of AN significantly reduced the cell viability and cell survival of skin cancer cell lines, achieved by MTT assay and clonogenic assays, respectively...
December 2016: 3 Biotech
https://www.readbyqxmd.com/read/28319728/modulation-of-host-cell-apoptotic-pathways-by-intracellular-pathogens
#2
REVIEW
Anja Friedrich, Julian Pechstein, Christian Berens, Anja Lührmann
Nearly all steps of the host cell apoptotic cascade can be subverted by intracellular microorganisms. Some pathogens modulate early steps and interfere with sensing of extracellular signals, cellular stress or signal transduction; others target Bcl-2 proteins, caspases, or inhibitor of apoptosis proteins (IAPs). In many cases the exact molecular mechanisms leading to interference with the host cell apoptotic cascade are still unknown. However, there are some examples where bacterial factors that modulate host cell death have been identified...
March 17, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/28315432/splicing-factors-of-sr-and-hnrnp-families-as-regulators-of-apoptosis-in-cancer
#3
Hanna Kędzierska, Agnieszka Piekiełko-Witkowska
SR and hnRNP proteins were initially discovered as regulators of alternative splicing: the process of controlled removal of introns and selective joining of exons through which multiple transcripts and, subsequently, proteins can be expressed from a single gene. Alternative splicing affects genes involved in all crucial cellular processes, including apoptosis. During cancerogenesis impaired apoptotic control facilitates survival of cells bearing molecular aberrations, contributing to their unrestricted proliferation and chemoresistance...
March 14, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28315173/ricolinostat-a-selective-hdac6-inhibitor-shows-anti-lymphoma-cell-activity-alone-and-in-combination-with-bendamustine
#4
Maria Cosenza, Monica Civallero, Luigi Marcheselli, Stefano Sacchi, Samantha Pozzi
Histone deacetylase inhibitors (HDACis) have emerged as a new class of anticancer agents, targeting the biological process including cell cycle and apoptosis. We investigated and explained the anticancer effects of an HDAC6 inhibitor, ricolinostat alone and in combination with bendamustine in lymphoma cell lines. Cell viability was measured by MTT assay. Apoptosis, reactive oxygen species (ROS) generation, Bcl-2 protein expression, cell cycle progression and tubuline expression were determined by flow cytometry...
March 17, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28314430/calf-spleen-extractive-injection-csei-a-small-peptides-enriched-extraction-induces-human-hepatocellular-carcinoma-cell-apoptosis-via-ros-mapks-dependent-mitochondrial-pathway
#5
Dongxu Jia, Wenqian Lu, Xinrui Zhang, Guangsheng Cai, Lirong Teng, Xinyu Wang, Minghai Zhang, Yan Zeng, Chunhua Liang, Di Wang
Calf Spleen Extractive Injection (CSEI), a small peptides enriched extraction, performs immunomodulatory activity on cancer patients suffering from radiotherapy or chemotherapy. The present study aims to investigate the anti-hepatocellular carcinoma effects of CSEI in cells and tumor-xenografted mouse models. In HepG2 and SMMC-7721 cells, CSEI reduced cell viability, enhanced apoptosis rate, caused reactive oxygen species (ROS) accumulation, inhibited migration ability, and induced caspases cascade and mitochondrial membrane potential dissipation...
October 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28306533/ros-mediated-induction-of-apoptosis-by-benzoquinone-embelin-in-human-colon-adenocarcinoma-cells-ht-29
#6
Kodandaram Sumalatha, Mohan Gowda, Sreepriya Meenakshisundaram
Background Embelin is a benzoquinone reported to possess anticancer activity in several in vivo and in vitro models of carcinogenesis, especially hematopoietic and prostate malignancy. A detailed investigation on the influence of embelin on epithelial malignancy model system, especially colon adenocarcinoma, is lacking. The objective of the current study is to investigate the antiproliferative, antiinvasive and proapoptotic potential of embelin on colon adenocarcinoma cell line HT-29. Methods The effect of embelin (35 µg/mL for 24 h) on cell proliferation was assessed by Sulforhodamine B assay and bromodeoxyuridine incorporation test, antiinvasive effect by Boyden chamber assay and scratch assay...
March 17, 2017: Journal of Complementary & Integrative Medicine
https://www.readbyqxmd.com/read/28301598/regulation-of-anti-apoptotic-bcl-2-family-protein-mcl-1-by-s6-kinase-2
#7
Alakananda Basu, Savitha Sridharan
The anti-apoptotic Bcl-2 family protein myeloid cell leukemia-1 (Mcl-1) plays an important role in breast cancer cell survival and chemoresistance. We have previously shown that knockdown of the 40S ribosomal protein S6 kinase-2 (S6K2), which acts downstream of the mechanistic target of rapamycin complex 1 (mTORC1), enhanced breast cancer cell death by apoptotic stimuli. The increase in cell death by S6K2 depletion was partly due to inactivation of Akt. In the present study, we investigated if S6K2 regulates Mcl-1, which acts downstream of Akt...
2017: PloS One
https://www.readbyqxmd.com/read/28298211/fty720-inhibits-mesothelioma-growth-in-vitro-and-in-a-syngeneic-mouse-model
#8
Agata Szymiczek, Sandra Pastorino, David Larson, Mika Tanji, Laura Pellegrini, Jiaming Xue, Shuangjing Li, Carlotta Giorgi, Paolo Pinton, Yasutaka Takinishi, Harvey I Pass, Hideki Furuya, Giovanni Gaudino, Andrea Napolitano, Michele Carbone, Haining Yang
BACKGROUND: Malignant mesothelioma (MM) is a very aggressive type of cancer, with a dismal prognosis and inherent resistance to chemotherapeutics. Development and evaluation of new therapeutic approaches is highly needed. Immunosuppressant FTY720, approved for multiple sclerosis treatment, has recently raised attention for its anti-tumor activity in a variety of cancers. However, its therapeutic potential in MM has not been evaluated yet. METHODS: Cell viability and anchorage-independent growth were evaluated in a panel of MM cell lines and human mesothelial cells (HM) upon FTY720 treatment to assess in vitro anti-tumor efficacy...
March 15, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28295507/crocin-suppresses-constitutively-active-stat3-through-induction-of-protein-tyrosine-phosphatase-shp-1
#9
Buyun Kim, Ki Yong Lee, Byoungduck Park
The aim of the present study is to investigate the effect of a natural compound crocin, one of the active components of saffron, on human multiple myeloma cells. Crocin effectively suppressed constitutive STAT3 activation, translocation of STAT3 to the nucleus, and its target gene expression. The suppression of STAT3 was mediated through the inhibition of activation of protein tyrosine kinases JAK1, JAK2 and c-Src. We found that crocin induced the expression of SHP-1, a tyrosine protein phosphatase, and pervanadate treatment reversed the crocin-induced downregulation of STAT3, suggesting the involvement of a protein tyrosine phosphatase...
March 10, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28290146/cyclooxygenase-2-directs-microglial-activation-mediated-inflammation-and-oxidative-stress-leading-to-intrinsic-apoptosis-in-zn-induced-parkinsonism
#10
Amit Kumar Chauhan, Namrata Mittra, Devendra Kumar Patel, Chetna Singh
Inflammation is decisive in zinc (Zn)-induced nigrostriatal dopaminergic neurodegeneration; however, the contribution of cyclooxygenase-2 (COX-2) is not yet known. The present study aimed to explore the role of COX-2 in Zn-induced Parkinsonism and its association with the microglial activation. Male Wistar rats were treated intraperitoneally (i.p.) with Zn as zinc sulphate (20 mg/kg) along with respective controls for 2-12 weeks. In a few sets, animals were also treated with/without celecoxcib (CXB, 20 mg/kg, i...
March 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28289901/overexpression-of-rsf-1-correlates-with-poor-survival-and-promotes-invasion-in-non-small-cell-lung-cancer
#11
Xiuwei Zhang, Lin Fu, Dongwei Xue, Xiupeng Zhang, Fengxia Hao, Lingling Xie, Jiani He, Junda Gai, Yuhui Liu, Hongtao Xu, Qingchang Li, Enhua Wang
Rsf-1 (HBXAP) was recently reported to play roles in tumorigenesis and tumor progression. There have been many reports referred to Rsf-1 overexpression in various cancers and associated with the malignant behavior of cancer cells. However, the molecular mechanism of Rsf-1 in non-small cell lung cancer aggressiveness remains ambiguous. In the present study, we found that there was a significant association between Rsf-1 overexpression and poor overall survival (p = 0.028) in lung cancer. Furthermore, knockdown of Rsf-1 expression in H1299 and H460 cells with high endogenous Rsf-1 expression inhibited cell migration and invasion and downregulated MMP2 expression and nuclear levels of NF-κB...
March 13, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28289414/podophyllotoxin-and-rutin-modulates-ionizing-radiation-induced-oxidative-stress-and-apoptotic-cell-death-in-mice-bone-marrow-and-spleen
#12
Abhinav Singh, M H Yashavarddhan, Bhargab Kalita, Rajiv Ranjan, Sania Bajaj, Hridayesh Prakash, Manju Lata Gupta
The present study is aimed to investigate the radioprotective efficacy of G-003M (combination of podophyllotoxin and rutin) against gamma radiation-induced oxidative stress and subsequent cell death in mice bone marrow and spleen. Prophylactic administration of G-003M (-1 h) rendered more than 85% survival in mice exposed to 9 Gy (lethal dose) with dose reduction factor of 1.26. G-003M pretreated mice demonstrated significantly reduced level of reactive oxygen species, membrane lipid peroxidation, and retained glutathione level...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28288819/multifaceted-anticancer-activity-of-bh3-mimetics-current-evidence-and-future-prospects
#13
REVIEW
Małgorzata Opydo-Chanek, Oscar Gonzalo, Isabel Marzo
BH3 mimetics are a novel class of anticancer agents designed to specifically target pro-survival proteins of the Bcl-2 family. Like endogenous BH3-only proteins, BH3 mimetics competitively bind to surface hydrophobic grooves of pro-survival Bcl-2 family members, counteracting their protective effects and thus facilitating apoptosis in cancer cells. Among the small-molecule BH3 mimetics identified, ABT-737 and its analogs, obatoclax as well as gossypol derivatives are the best characterized. The anticancer potential of these compounds applied as a single agent or in combination with chemotherapeutic drugs is currently being evaluated in preclinical studies and in clinical trials...
March 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28281963/microrna-1284-inhibits-cell-viability-and-induces-apoptosis-of-ovarian-cancer-cell-line-ovcar3
#14
Changqing Pan, Dan Wang, Yao Zhang, Wenliang Yu
Ovarian cancer is a malignancy with high mortality among women. Multiple reports show that microRNAs (miRs) act as regulators in ovarian cancer inhibition, while the role of miR-1284 in ovarian cancer is still unknown. This study aimed to investigate the effects of miR-1284 on ovarian cancer cells. Human ovarian cancer cell line OVCAR3 was cultured and transfected with miR-1284 mimics, inhibitors, or control. Viability and apoptosis of transfected cells were then determined by MTT assay, BrdU assay, and flow cytometry...
October 27, 2016: Oncology Research
https://www.readbyqxmd.com/read/28281186/calcium-sensing-receptor-mediated-mitogen-activated-protein-kinase-pathway-improves-the-status-of-transplanted-mouse-embryonic-stem-cells-in-rats-with-acute-myocardial-infarction
#15
Jian Sun, Tao Wei, Shuzhi Bai, Hongtao Zhao, Xiaoqin Liu, Jinfeng Yu, Li Li, Gaochen Song, Hairong Luan, Changqing Xu
Several studies have identified the critical role of calcium-sensing receptors (CaSRs) in cardiac ischaemia/reperfusion injury and cardiac hypertrophy and have demonstrated that CaSRs induce myocardial apoptosis by activating MAPKs. Using acute myocardial infarction rat models, we found that a combination therapy of CaSR inhibition and embryonic stem cell (ESC) transplantation after acute myocardial infarction (AMI) leads to a dramatic reduction in the infarct size; a significant increase in the maximum rising and falling rate (+dp/dtmax and -dp/dtmax, respectively) of left ventricular pressure; a significant decrease in left ventricular end-diastolic pressure; a significant decrease in the mRNA expression level of CaSR, Bax, Bcl-2, cleaved caspase-3, cleaved caspase-9, p-ERK, p-JNK and p-P38 protein together with apoptosis indexes in the C and E groups; and a significant decrease in cTnT levels as well as LDH and CK activity...
March 9, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28279820/binding-affinity-of-pro-apoptotic-bh3-peptides-for-the-anti-apoptotic-mcl-1-and-a1-proteins-molecular-dynamics-simulations-of-mcl-1-and-a1-in-complex-with-six-different-bh3-peptides
#16
Vivek Modi, Ramasubbu Sankararamakrishnan
The anti-apoptotic members of Bcl-2 family of proteins bind to their pro-apoptotic counterparts to induce or prevent cell death.Based on the distinct binding profiles for specific pro-apoptotic BH3 peptides, the anti-apoptotic Bcl-2 proteins can be divided into at least two subclasses. The subclass that includes Bcl-XL binds strongly to Bad BH3 peptide while it has weak binding affinity for the second subclass of Bcl-2 proteins such as Mcl-1 and A1. Anti-apoptotic Bcl-2 proteins are considered to be attractive drug targets for anti-cancer drugs...
February 9, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28275031/nccn-guidelines-insights-chronic-lymphocytic-leukemia-small-lymphocytic-leukemia-version-1-2017
#17
William G Wierda, Andrew D Zelenetz, Leo I Gordon, Jeremy S Abramson, Ranjana H Advani, C Babis Andreadis, Nancy Bartlett, John C Byrd, Paolo Caimi, Luis E Fayad, Richard I Fisher, Martha J Glenn, Thomas M Habermann, Nancy Lee Harris, Francisco Hernandez-Ilizaliturri, Richard T Hoppe, Steven M Horwitz, Mark S Kaminski, Christopher R Kelsey, Youn H Kim, Susan Krivacic, Ann S LaCasce, Michael G Martin, Auayporn Nademanee, Pierluigi Porcu, Oliver Press, Rachel Rabinovitch, Nishitha Reddy, Erin Reid, Kenneth Roberts, Ayman A Saad, Erin D Snyder, Lubomir Sokol, Lode J Swinnen, Julie M Vose, Joachim Yahalom, Mary A Dwyer, Hema Sundar
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are different manifestations of the same disease and managed in much the same way. The advent of novel CD20 monoclonal antibodies led to the development of effective chemoimmunotherapy regimens. More recently, small molecule inhibitors targeting kinases involved in a number of critical signaling pathways and a small molecule inhibitor of the BCL-2 family of proteins have demonstrated activity for the treatment of patients with CLL/SLL. These NCCN Guidelines Insights highlight important updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for CLL/SLL for the treatment of patients with newly diagnosed or relapsed/refractory CLL/SLL...
March 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28267674/the-effects-of-saha-on-radiosensitivity-in-pancreatic-cancer-cells-by-inducing-apoptosis-and-targeting-rad51
#18
Zhibing Wu, Saisai Jing, Yanhong Li, Yabo Gao, Shuhuan Yu, Zhitian Li, Yanyan Zhao, Jigang Piao, Shenglin Ma, Xufeng Chen
Suberoyl anilide hydroxamic acid (SAHA) is one of the most promising Histone deacetylases(HDAC) inhibitors which has shown significant anti-tumor activity for many malignancies. We explored the potential mechanism of the radiosensitivity effect of SAHA in Panc-1 cells and attempted to develop SAHA as a systemic treatment strategy for pancreatic cancer. Growth inhibition was detected by CCK-8 assay. Radiosensitizing enhancement ratio was determined by clonogenic assay. The cell cycle and apoptosis assay was detected using flow cytometry and annexin-V/PI...
March 3, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28266177/tnf-%C3%AE-promotes-survival-and-migration-of-mscs-under-oxidative-stress-via-nf-%C3%AE%C2%BAb-pathway-to-attenuate-intimal-hyperplasia-in-vein-grafts
#19
Xiao Bai, Jie Xi, Yanwen Bi, Xin Zhao, Weidong Bing, Xiangbin Meng, Yimin Liu, Zhonglai Zhu, Guangmin Song
The oxidative stress caused by endothelial injury is involved in intimal hyperplasia (IH) in vein grafts. Mesenchymal stem cells (MSCs) can home to injured intima and promote endothelial repair. However, MSC apoptosis is increased accompanied by decreased functional activity under oxidative stress. Thus, we investigate whether tumour necrosis factor-α (TNF-α) can promote the survival and activity of MSCs under oxidative stress to reduce IH more effectively, and establish what role the NF-κB pathway plays in this...
March 7, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28265066/resistance-mechanisms-to-tp53-mdm2-inhibition-identified-by-in-vivo-piggybac-transposon-mutagenesis-screen-in-an-arf-mouse-model
#20
Emilie A Chapeau, Agnieszka Gembarska, Eric Y Durand, Emeline Mandon, Claire Estadieu, Vincent Romanet, Marion Wiesmann, Ralph Tiedt, Joseph Lehar, Antoine de Weck, Roland Rad, Louise Barys, Sebastien Jeay, Stephane Ferretti, Audrey Kauffmann, Esther Sutter, Armelle Grevot, Pierre Moulin, Masato Murakami, William R Sellers, Francesco Hofmann, Michael Rugaard Jensen
Inhibitors of double minute 2 protein (MDM2)-tumor protein 53 (TP53) interaction are predicted to be effective in tumors in which the TP53 gene is wild type, by preventing TP53 protein degradation. One such setting is represented by the frequent CDKN2A deletion in human cancer that, through inactivation of p14ARF, activates MDM2 protein, which in turn degrades TP53 tumor suppressor. Here we used piggyBac (PB) transposon insertional mutagenesis to anticipate resistance mechanisms occurring during treatment with the MDM2-TP53 inhibitor HDM201...
March 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
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