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https://www.readbyqxmd.com/read/29054108/increase-in-pro-apoptotic-activity-of-inhibitory-pas-domain-protein-via-phosphorylation-by-mk2
#1
Shuya Kasai, Mary Jane Elizabeth Richardson, Satoru Torii, Ken-Ichi Yasumoto, Hiroki Shima, Kazuhiko Igarashi, Ken Itoh, Kazuhiro Sogawa, Kazutaka Murayama
Inhibitory PAS domain protein (IPAS) is a bifunctional protein that downregulates hypoxic gene expression and exerts pro-apoptotic activity by preventing pro-survival activity of Bcl-xL and its related factors. Pro-apoptotic activity of IPAS is attenuated by the activation of the PINK1-Parkin pathway, and involved in neuronal degeneration in an experimental mouse model of Parkinson's disease. The current study shows that phosphorylation of IPAS at Ser184 by MAPK-activated protein kinase 2 (MK2 or MAPKAPK2) enhances the pro-apoptotic function of IPAS...
October 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29053012/the-ratio-of-thioredoxin-keap1-protein-level-is-a-predictor-of-distant-metastasis-in-colorectal-cancer
#2
Liang-Che Chang, Chung-Wei Fan, Wen-Ko Tseng, Hui-Ping Chein, Tsan-Yu Hsieh, Jim-Ray Chen, Cheng-Cheng Hwang, Chung-Ching Hua
AIM: Thioredoxin can reduce the cysteine group of Keap1 which could induce proteasome degradation of Nrf2, PGAM5 and Bcl-xL. Nrf2 regulates redox balance and Bcl-xL is anti-apoptotic and both are important in tumor progression. METHODS: The protein levels of Keap1, thioredoxin, PGAM5 and Bcl-xL in the normal and tumor tissues of 64 subjects with colorectal cancer (CRC) were determined by western blot. RESULTS: The tumor had higher Keap1 but lower PGAM5s and Bcl-xL protein expression than the normal tissue...
October 20, 2017: Biomarkers in Medicine
https://www.readbyqxmd.com/read/29050266/physapubescin-b-inhibits-tumorgenesis-and-circumvents-taxol-resistance-of-ovarian-cancer-cells-through-stat3-signaling
#3
Xiaofeng Zhao, Lu Huang, Wanwan Xu, Xiaoyan Chen, Yan Shen, Wenjie Zeng, Xiao Chen
Ovarian cancer is the most lethal gynaecological malignancy. Recurrence and subsequent resistance to chemotherapy have become major obstacles to treating these diseases. In the present study, we showed that a natural withanolide isolated from the plant Physalis pubescens L. (Solanaceae), Physapubescin B, exhibited potent anti-tumor activity against ovarian cancer cells. Physapubescin B promoted apoptosis, induced cell-cycle arrest and inhibited invasion of ES-2 and A2780 cells. Physapubescin B treatment also resulted in suppression of the transcriptional activity of STAT3, an oncogenic transcription factor activated in many human malignancies including ovarian cancer, through disturbing the dimerization of STAT3, and thereby inhibited the nuclear translocation of Tyr705/Ser727-phosphorylated STAT3...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050265/reactive-oxygen-species-dependent-phosphorylation-of-the-liver-kinase-b1-amp-activated-protein-kinase-acetyl-coa-carboxylase-signaling-is-critically-involved-in-apoptotic-effect-of-lambertianic-acid-in-hepatocellular-carcinoma-cells
#4
Arong Jeong, Ju-Ha Kim, Hyo-Jung Lee, Sung-Hoon Kim
Though lambertianic acid (LA) is reported to have hypolipidemic activity in liver, its underlying anticancer mechanism is poorly understood so far. Thus, in the present study, apoptotic mechanism of LA was elucidated in HepG2 and SK-Hep1 hepatocellular carcinoma (HCC) cells. Here LA increased cytotoxicity, sub-G1 population and Annexin V/PI positive cells in two HCC cells. Also, LA cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP), activated phosphorylation of liver kinase B1 (LKB1)/AMP activated protein kinase (AMPK)/ acetyl-CoA carboxylase (ACC) pathway and also suppressed antiapoptotic proteins such as phosphorylation of Akt/ mammalian target of rapamycin (mTOR) and the expression of B cell lymphoma-2 (Bcl-2)/ B-cell lymphoma-extra large (Bcl-xL) and cyclooxygenase-2 (COX-2) in two HCC cells...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29049036/histone-deacetylase-inhibitor-bg45-mediated-ho-1-expression-induces-apoptosis-of-multiple-myeloma-cells-by-the-jak2-stat3-pathway
#5
Sishi Tang, Bingqing Cheng, Nana Zhe, Dan Ma, Jibing Xu, Xinyao Li, Yongling Guo, Weibing Wu, Jishi Wang
Multiple myeloma (MM) is a hematological malignancy that is characterized by the clonal expansion of plasma cells in the bone marrow. Histone deacetylases (HDACs) represent a new type of molecular targeted therapy for different types of cancers and promising targets for myeloma therapy. We showed that HDAC3 mRNA and protein levels of CD138 mononuclear cells from MM patients were higher than those in healthy donors. Therefore, we investigated the effects of a novel class I HDAC inhibitor BG45 on MM cells in vitro...
October 18, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29048645/establishment-and-characterization-of-human-osteosarcoma-cells-resistant-to-pyropheophorbide-%C3%AE-methyl-ester-mediated-photodynamic-therapy
#6
Yong Tao, Yunsheng Ou, Hang Yin, Yanyang Chen, Shenxi Zhong, Yongjian Gao, Zenghui Zhao, Bin He, Qiu Huang, Qianxing Deng
The present study was performed to establish and characterize new human osteosarcoma cell lines resistant to pyropheophorbide-α methyl ester‑mediated photodynamic therapy (MPPa-PDT). MPPa-PDT-resistant cells are isolated from the human osteosarcoma MG63 and HOS cell lines and two resistant populations were finally acquired, including MG63/PDT and HOS/PDT. Cell Counting Kit-8 (CCK-8) assay was used to determine the MPPa-PDT, cisplatin (CDDP) resistance and proliferation of MG63, MG63/PDT, HOS and HOS/PDT cells...
September 27, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29048633/in%C3%A2-vitro-and-in%C3%A2-vivo-anti-primary-effusion-lymphoma-activities-of-fucoidan-extracted-from-cladosiphon-okamuranus-tokida
#7
Chie Ishikawa, Naoki Mori
Primary effusion lymphoma (PEL) caused by Kaposi's sarcoma-associated herpesvirus (KSHV) is characterized by lymphomatous effusion in body cavities and poor prognosis. There is still no effective treatment for PEL. Fucoidan, a major sulfated polysaccharide isolated from brown seaweeds, has an attractive array of bioactivities such as cancer inhibition. However, the effects of fucoidan on PEL cells remain unclear. We investigated the anti-PEL effects of fucoidan obtained from Cladosiphon okamuranus Tokida cultivated in Okinawa...
September 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29047155/maduramicin-induces-apoptosis-and-necrosis-and-blocks-autophagic-flux-in-myocardial-h9c2-cells
#8
Xin Chen, Long Chen, Shanxiang Jiang, Shile Huang
Maduramicin, a polyether ionophore antibiotic, is widely used as an anticoccidial agent in the poultry industry. It has been reported that maduramicin may cause heart and skeletal muscle cell damage, resulting in heart failure, skeletal muscle degeneration and even death in animals and humans, if improperly used. However, the molecular mechanism behind its capability to cause death of cardiac cells is not known. Here, we show that maduramicin induced apoptosis and necrosis in rat myocardial cells (H9c2). Maduramicin did not apparently upregulate the expression of pro-apoptotic proteins (e...
October 19, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29045576/activation-of-cannabinoid-receptor-1-is-involved-in-protection-against-mitochondrial-dysfunction-and-cerebral-ischaemic-tolerance-induced-by-isoflurane-preconditioning
#9
M Cai, Q Yang, G Li, S Sun, Y Chen, L Tian, H Dong
Background: Isoflurane preconditioning (IPC) induces cerebral ischaemic tolerance, but the mechanism remains poorly understood. The aim of this study was to determine changes in mitochondrial function in the brain after IPC, and whether the cannabinoid receptor 1 (CB1R) could be involved in the mechanism of mitochondrial protection mediated by IPC. Methods: Adult male Sprague-Dawley rats were pretreated with isoflurane 2% for 1 h day-1, for 5 days consecutively, and then subjected to 120 min right middle cerebral artery occlusion...
October 13, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29040496/changes-in-platelet-bax-levels-contribute-to-impaired-platelet-response-to-thrombin-after-cardiopulmonary-bypass-prospective-observational-clinical-and-laboratory-investigations
#10
M Murase, Y Nakayama, D I Sessler, N Mukai, S Ogawa, Y Nakajima
Background: Anucleate platelets can undergo apoptosis in response to various stimuli, as do nucleated cells. Cardiopulmonary bypass (CPB) causes platelet dysfunction and can also activate platelet apoptotic pathways. We therefore evaluated time-dependent changes in blood platelet Bax (a pro-apoptotic molecule) levels and platelet dysfunction after cardiac surgery. Methods: We assessed blood samples obtained from subjects having on-pump or off-pump coronary artery bypass graft surgery (n=20 each)...
October 10, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29039568/3-3-%C3%A2-diindolylmethane-attenuates-cardiomyocyte-hypoxia-by-modulating-autophagy-in-h9c2-cells
#11
Kai Liang, Wen-Hao Qian, Jing Zong
Autophagy is activated in the ischemic heart and is a process that is essential for survival, differentiation, development and homeostasis. 3,3'‑Diindolylmethane (DIM) is a natural product of the acid‑catalyzed condensation of indole‑3‑carbinol in cruciferous vegetables. Numerous studies have suggested that DIM has various pharmacological effects, including antioxidant, antitumor, anti‑angiogenic and anti‑apoptotic properties. However, the function of DIM on hypoxia‑induced cardiac injury remains to be elucidated...
October 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29035884/protective-effects-of-pretreatment-with-quercetin-against-lipopolysaccharide-induced-apoptosis-and-the-inhibition-of-osteoblast-differentiation-via-the-mapk-and-wnt-%C3%AE-catenin-pathways-in-mc3t3-e1-cells
#12
Chun Guo, Rui-Juan Yang, Ke Jang, Xiao-Ling Zhou, Yu-Zhen Liu
BACKGROUND/AIMS: Quercetin, a flavonoid found in onions and other vegetables, has potential inhibitory effects on bone resorption in vivo and in vitro. In our previous study, we found that quercetin treatment reversed lipopolysaccharide (LPS)-induced inhibition of osteoblast differentiation through the mitogen-activated protein kinase (MAPK) pathway in MC3T3-E1 cells. In this study, we investigated the underlying mechanisms of pretreatment with quercetin on apoptosis and the inhibition of osteoblast differentiation in MC3T3-E1 cells induced by LPS...
October 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29035366/cytoplasmic-p53-couples-oncogene-driven-glucose-metabolism-to-apoptosis-and-is-a-therapeutic-target-in-glioblastoma
#13
Wilson X Mai, Laura Gosa, Veerle W Daniels, Lisa Ta, Jonathan E Tsang, Brian Higgins, W Blake Gilmore, Nicholas A Bayley, Mitra Dehghan Harati, Jason T Lee, William H Yong, Harley I Kornblum, Steven J Bensinger, Paul S Mischel, P Nagesh Rao, Peter M Clark, Timothy F Cloughesy, Anthony Letai, David A Nathanson
Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models...
October 9, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29034364/microenvironmental-agonists-generate-de-novo-phenotypic-resistance-to-combined-ibrutinib-plus-venetoclax-in-cll-and-mcl
#14
Kallesh D Jayappa, Craig A Portell, Vicki L Gordon, Brian J Capaldo, Stefan Bekiranov, Mark J Axelrod, L Kyle Brett, Julia D Wulfkuhle, Rosa I Gallagher, Emanuel F Petricoin, Timothy P Bender, Michael E Williams, Michael J Weber
De novo resistance and rapid recurrence often characterize responses of B-cell malignancies to ibrutinib (IBR), indicating a need to develop drug combinations that block compensatory survival signaling and give deeper, more durable responses. To identify such combinations, we previously performed a combinatorial drug screen and identified the Bcl-2 inhibitor venetoclax (VEN) as a promising partner for combination with IBR in Mantle Cell Lymphoma (MCL). We have opened a multi-institutional clinical trial to test this combination...
June 13, 2017: Blood Advances
https://www.readbyqxmd.com/read/29033852/activation-of-casein-kinase-ii-by-gallic-acid-induces-bik-bax-bak-mediated-er-ca-ros-dependent-apoptosis-of-human-oral-cancer-cells
#15
Meng-Liang Lin, Shih-Shun Chen
Induction of the generation of endoplasmic reticulum (ER) calcium (Ca(++))-mediated reactive oxygen species (ROS) by gallic acid (GA) has been implicated in the mitochondrial apoptotic death of human oral cancer (OC) cells, but the molecular mechanism by which GA causes ER Ca(++) release of OC cells to undergo cell death remains unclear. Here, we report that GA-induced phosphorylation of B-cell lymphoma 2 (BCL-2)-interacting killer (BIK) (threonine (Thr) 33/Serine (Ser) 35) and p53 (Ser 15 and Ser 392), Bcl-2-associated x protein (BAX)/BCL-2 antagonist killer 1 (BAK) oligomerization on the ER and mitochondria, rising of cytosolic Ca(+)(+) and ROS, cytochrome c (Cyt c) release from the mitochondria, Ψm loss, and apoptosis were suppressed in cells co-treated with a specific inhibitor of casein kinase II (CK II) (4,5,6,7-tetrabromobenzotriazole)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29031805/aptamer-targeted-delivery-of-bcl-xl-shrna-using-alkyl-modified-pamam-dendrimers-into-lung-cancer-cells
#16
Sara Ayatollahi, Zahra Salmasi, Maryam Hashemi, Saeedeh Askarian, Reza Kazemi Oskuee, Khalil Abnous, Mohammad Ramezani
RNAi-based gene therapy has been recently considered as a promising approach against cancer. Targeted delivery of drug, gene or therapeutic RNAi-based systems to tumor cells is one of the important issues in order to reduce side effects on normal cells. Several strategies have been developed to improve the safety and selectivity of cancer treatments including antibodies, peptides and recently aptamers with various attractive characteristics including higher target specificity, affinity and reduced toxicity...
October 11, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29029479/the-genetically-engineered-drug-rhcnb-induces-apoptosis-via-a-mitochondrial-route-in-tumor-cells
#17
Yang Yang, Huan Yang, Jinju Yang, Li Li, Benqiong Xiang, Qun Wei
The calcineurin B subunit (CNB) has antitumor activity. We showed previously that recombinant human CNB (rhCNB) also had strong anti-tumor activity in vivo, and was thus a promising candidate anti-tumor drug. It appeared to kill tumor cells via immunomodulation. Here, we show that rhCNB inhibits the proliferation of human hepatoma HepG-2 cells, resulting in their apoptosis. Exogenous CNB was found to localize to mitochondria in tumor cells and activate the mitochondrial apoptosis pathway, as indicated by a decrease of mitochondrial transmembrane potential, release of cytochrome C and activation of caspase-9, which then activates caspase-3...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29022011/placental-extract-ameliorates-non-alcoholic-steatohepatitis-nash-by-exerting-protective-effects-on-endothelial-cells
#18
Akihiro Yamauchi, Akiko Kamiyoshi, Teruhide Koyama, Nobuyoshi Iinuma, Shumpei Yamaguchi, Hiroyuki Miyazaki, Eiichi Hirano, Taiichi Kaku, Takayuki Shindo
Non-alcoholic steatohepatitis (NASH) is a severe form of fatty liver disease that is defined by the presence of inflammation and fibrosis, ultimately leading to cirrhosis and hepatocellular carcinoma. Treatment with human placental extract (HPE) reportedly ameliorates the hepatic injury. We evaluated the effect of HPE treatment in a mouse model of NASH. In the methione- and choline-deficient (MCD) diet-induced liver injury model, fibrosis started from regions adjacent to the sinusoids. We administered the MCD diet with high-salt loading (8% NaCl in the drinking water) to mice deficient in the vasoprotective molecule RAMP2 for 5 weeks, with or without HPE...
September 2017: Heliyon
https://www.readbyqxmd.com/read/29021786/a-new-role-for-helicobacter-pylori-urease-contributions-to-angiogenesis
#19
Deiber Olivera-Severo, Augusto F Uberti, Miguel S Marques, Marta T Pinto, Maria Gomez-Lazaro, Céu Figueiredo, Marina Leite, Célia R Carlini
Helicobacter pylori is a pathogen involved in gastric diseases such as ulcers and carcinomas. H. pylori's urease is an important virulence factor produced in large amounts by this bacterium. In previous studies, we have shown that this protein is able to activate several cell types like neutrophils, monocytes, platelets, endothelial cells, and gastric epithelial cells. Angiogenesis is a physiological process implicated in growth, invasion and metastization of tumors. Here, we have analyzed the angiogenic potential of H...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29020881/knockdown-of-reg%C3%AE-inhibits-the-proliferation-and-migration-and-promotes-the-apoptosis-of-multiple-myeloma-cells-by-downregulating-nf-%C3%AE%C2%BAb-signal-pathway
#20
Shuang Liu, Li-Ling Zheng, Yang-Min Zhu, Hui-Juan Shen, Qi Zhong, Jing Huang, Cheng Li, Zhi Liu, Meng-Dong Yao, Rui-Ming Ou, Qing Zhang
OBJECTIVES: This study aimed to evaluate the effects of REGγ knockdown on the proliferation, apoptosis and migration of multiple myeloma (MM) cells, and reveal the potential regulatory mechanisms. METHODS: The expression of REGγ on myeloma cells of 28 MM patients was detected by Western blot. shRNA-REGγ-1 and shRNA-REGγ-2 were constructed to downregulate REGγ in RPMI-8226 cells. The proliferation, apoptosis and migration of transfected cells were analyzed by Cell Counting Kit 8 (CCK8), flow cytometry and transwell chamber, respectively...
October 11, 2017: Hematology (Amsterdam, Netherlands)
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