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Apoptosis therapy

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https://www.readbyqxmd.com/read/29454280/8-chrysoeriol-as-a-potential-bcl-2-inhibitor-triggers-apoptosis-of-sw1990-pancreatic-cancer-cells
#1
Yiwen Zhang, Zhimei Li, Qiuxia Min, Abulizi Palida, Yiyuan Zhang, Ruotian Tang, Lixia Chen, Hua Li
8-Chrysoeriol, a bioactive flavanoid, was firstly identified to bind directly to BCL-2 as BH3 mimetics by structure-based virtual ligand screening. And 3D docking model revealed the molecular basis of 8-Chrysoeriol targeting to BCL-2. The interaction between 8-Chrysoeriol and BCL-2 was further confirmed using Microscale Thermophoresis (MST) technique. Meanwhile, high expression level of antiapoptotic protein BCL-2 was detected in SW1990 pancreatic cancer cells and 8-Chrysoeriol showed obvious proapoptosis effect against SW1990 in vitro...
February 2, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29454261/frequency-of-somatic-tp53-mutations-in-combination-with-known-pathogenic-mutations-in-colon-adenocarcinoma-non-small-cell-lung-carcinoma-and-gliomas-as-identified-by-next-generation-sequencing
#2
Zahra Shajani-Yi, Francine B de Abreu, Jason D Peterson, Gregory J Tsongalis
The tumor suppressor gene TP53 is the most frequently mutated gene in human cancer. It encodes p53, a DNA-binding transcription factor that regulates multiple genes involved in DNA repair, metabolism, cell cycle arrest, apoptosis, and senescence. TP53 is associated with human cancer by mutations that lead to a loss of wild-type p53 function as well as mutations that confer alternate oncogenic functions that enable them to promote invasion, metastasis, proliferation, and cell survival. Identifying the discrete TP53 mutations in tumor cells may help direct therapies that are more effective...
February 13, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29453900/downregulation-of-reticulocalbin-1-differentially-facilitates-apoptosis-and-necroptosis-in-human-prostate-cancer-cells
#3
Xiaofei Liu, Nianzhao Zhang, Dawei Wang, Deyu Zhu, Quan Yuan, Xiulei Zhang, Lilin Qian, Huanmin Niu, Yi Lu, Guijie Ren, Keli Tian, Huiqing Yuan
Reticulocalbin 1 (RCN1), an endoplasmic reticulum (ER)-resident Ca 2+ -binding protein, is dysregulated in cancers, but its pathophysiological roles are largely unclear. Here, we demonstrate that RCN1 is overexpressed in clinical prostate cancer (PCa) samples, associated with Cyclin B, not Cyclin D1 expression, compared to that of benign tissues in a Chinese Han population. Downregulation of endogenous RCN1 significantly suppresses PCa cell viability and arrests the cell cycles of DU145 and LNCaP cells at the S and G2/M phases, respectively...
February 17, 2018: Cancer Science
https://www.readbyqxmd.com/read/29453896/the-anti-malarial-mefloquine-inhibits-nf-%C3%AE%C2%BAb-signaling-and-induces-apoptosis-in-colorectal-cancer-cells
#4
Xin Xu, Jun Wang, Kunkun Han, Shaoyan Li, Feng Xu, Yili Yang
The NF-κB signaling pathway is activated in many colorectal cancer (CRC) cells and in the tumor microenvironment, which plays a critical role in cancer initiation, development, and response to therapies. We found in the present study that the widely used antimalarial drug mefloquine was a NF-κB inhibitor that blocked the activation of IκBα kinase, leading to the reduction of IκBα degradation, decrease of p65 phosphorylation, and suppressed expression of NF-κB target genes in colorectal cancer cells. We also found that mefloquine induced growth arrest and apoptosis of colorectal cancer cells harboring phosphorylated p65 in culture and mice...
February 17, 2018: Cancer Science
https://www.readbyqxmd.com/read/29453833/ketamine-induces-apoptosis-in-lung-adenocarcinoma-cells-by-regulating-the-expression-of-cd69
#5
Xuhui Zhou, Peihong Zhang, Wei Luo, Lei Zhang, Rong Hu, Yu Sun, Hong Jiang
Ketamine, an anesthetic, analgesic, or sedative, is widely used for the treatment of cancer pain. Recently, ketamine has been also reported to be tumor repressor for inhibiting proliferation, invasion, and migration, and inducing apoptosis in many cancers. However, whether ketamine can induce the apoptosis of lung adenocarcinoma (LUAD) and which downstream molecular mediates its function remain largely unknown. A LUAD cell line A549 was incubated with ketamine at 0, 1, 10, and 100 μmol/L for 24 h. Trypan blue staining was used to detect the cell viability...
February 17, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29453543/toxic-and-beneficial-potential-of-silver-nanoparticles-the-two-sides-of-the-same-coin
#6
Lilian Rodrigues Rosa Souza, Veronica Santana da Silva, Leonardo Pereira Franchi, Tiago Alves Jorge de Souza
Nanotechnology has allowed great changes in chemical, biological and physical properties of metals when compared to their bulk counterparts. Within this context, silver nanoparticles (AgNPs) play a major role due to their unique properties, being widely used in daily products such as fabrics, washing machines, water filters, food and medicine. However, AgNPs can enter cells inducing a "Trojan-horse" type mechanism which potentially leads to cellular autophagy, apoptosis or necrosis. On the other hand, this cytotoxicity mechanism can be optimized to develop drug nanocarriers and anticancer therapies...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29453321/inhibition-of-cd95-cd95l-signaling-with-apg101-prevents-invasion-and-enhances-radiation-therapy-for-glioblastoma
#7
Jonas Blaes, Carina M Thomé, Philipp-Niclas Pfenning, Petra Rübmann, Felix Sahm, Antje Wick, Theresa Bunse, Torsten Schmenger, Jaromir Sykora, Andreas von Deimling, Benedikt Wiestler, Christian Merz, Manfred Jugold, Uwe Haberkorn, Amir Abdollahi, Jürgen Debus, Christian Gieffers, Claudia Kunz, Martin Bendszus, Michael Kluge, Michael Platten, Harald Fricke, Wolfgang Wick, Dieter Lemke
CD95 (Fas/APO-1), a death receptor family member, activity has been linked to tumorigenicity in multiple cancers, including glioblastoma multiforme (GBM). A phase II clinical trial on relapsed glioblastoma patients demonstrated that targeted inhibition of CD95 signaling via the CD95 ligand (CD95L) binding and neutralizing Fc-fusion protein APG101 (asunercept) prolonged patient survival. While CD95 signaling may be relevant for multiple aspects of tumor growth, the mechanism of action of APG101 in glioblastoma is not clear...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29452958/brca1-mutation-spectrum-functions-and-therapeutic-strategies-the-story-so-far
#8
REVIEW
Babita Sharma, Raman Preet Kaur, Sonali Raut, Anjana Munshi
BRCA1 gene mutations account for about 25-28% of hereditary Breast Cancer as BRCA1 is included in the category of high penetrance genes. Except for few commonmutations, there is a heterogenous spectrum of BRCA1 mutations in various ethnic groups. 185AGdel and 5382ins Care the most common BRCA1 alterations (founder mutations) which have been identified in most of the population. This review has been compiled with an aim to consolidate the information on genetic variants reported in BRCA1 found in various ethnic groups, their functional implications if known; involvement of BRCA1 in various cellular pathways/processes and potential BRCA1 targeted therapies...
January 8, 2018: Current Problems in Cancer
https://www.readbyqxmd.com/read/29452165/the-beneficial-role-of-early-exercise-training-following-stroke-and-possible-mechanisms
#9
REVIEW
Ying Xing, Si-Dong Yang, Fang Dong, Man-Man Wang, Ya-Shuo Feng, Feng Zhang
Exercise training is a regular therapy for stroke patients in clinic. However, whether the early exercise is beneficial for stroke patients is still controversial. The review was performed in databases of OVID, PUBMED, and ISI Web of Science, from respective inception to December 2017. In this review, we summarize the effect of different exercise intensity, initiation time, and style on ischemic stroke. Moreover, the possible mechanism is also discussed. The conclusion is that the voluntary exercise is better in promoting the functional recovery following stroke compared to forced exercise; too early initiated exercise might play a harmful role following stroke, while early initiated exercise might exert benefits after stroke; mild and moderate intensity exercise training could generate better neuroprotection in comparison with high intensity exercise training; early excise training could regulate the process of brain edema, cell apoptosis, oxidative damage, stem cells and other mechanisms in order to exert neuroprotection for brain...
February 13, 2018: Life Sciences
https://www.readbyqxmd.com/read/29451980/tri-layer-polymeric-shells-containing-magnetite-nanocarrier-mediated-lcs-1-delivery-for-synthetic-lethal-therapy-of-blm-defective-colorectal-cancer-cells
#10
Anuradha Gupta, Anas Ahmad, Hardeep Singh, Sharanjeet Kaur, Neethu K M, Md Meraj Ansari, Govindasamy Jayamurugan, Rehan Khan
Synthetic lethality is a molecular targeted therapy for selective killing of cancer cells. We exploited a lethal interaction between Superoxide dismutase1 inhibition and Bloom syndrome gene product (BLM) defect for the treatment of colorectal cancer (CRC) cells (HCT 116) with lung cancer screen-1 (LCS-1) loaded customized nanocarrier. LCS-1 has poor aqueous solubility. To overcome its limitations, customized nanocarrier (NC), composed of magnetite core coated with three polymeric shells namely, aminocellulose, branched poly(amidoamine) and paraben-PEG, was developed for encapsulating LCS-1...
February 16, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29451722/enhanced-photodynamic-therapy-by-reduced-intracellular-glutathione-levels-employing-nano-mof-with-cu-ii-as-active-center
#11
Wei Zhang, Jun Lu, Xiaonan Gao, Ping Li, Wen Zhang, Yu Ma, Hui Wang, Bo Tang
In photodynamic therapy (PDT), the level of reactive oxygen species (ROS) produced in the cell directly determines therapeutic effect. Therefore, the development of photosensitizers combining the ability of reducing GSH levels through synergistically improving ROS concentration to strengthen the efficacy of PDT for tumor is important. We report a nano-metal-organic framework based on Cu (II) as active center for PDT. This MOF-2 is readily uptaken by breast cancer cells, and high-level ROS is generated under light irradiation...
February 16, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29450644/pi3k-akt-inhibitor-ly294002-potentiates-homoharringtonine-antimyeloma-activity-in-myeloma-cells-adhered-to-stromal-cells-and-in-scid-mouse-xenograft
#12
Ping Chen, Xiaofang Wen, Bin Wang, Diyu Hou, Hong Zou, Qin Yuan, Hui Yang, Jieqiong Xie, Huifang Huang
Homoharringtonine (HHT) is a known anti-leukemia drug that inhibits multiple myeloma (MM) cells both in vitro and in vivo. Our prior study demonstrated that the potency of HHT in MM cells was compromised significantly when myeloma cells were co-cultured with BM stromal cells. This study aimed to investigate whether PI3K/Akt inhibitor LY294002 could potentiate the antimyeloma activity of HHT against MM cells adhered to BM stromal cells and in vivo xenograft models. A co-culture system composed of MM cells and human stromal cells was employed to mimic MM cells in bone marrow niche...
February 15, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29450633/mid1-pp2a-complex-functions-as-new-insights-in-human-lung-adenocarcinoma
#13
Lin Zhang, Junyao Li, Xuejiao Lv, Tingting Guo, Wei Li, Jie Zhang
PURPOSE: MID1 is an E3 ubiquitin ligase that was first found in Opitz G/BBB syndrome, but there has been little research into its role in lung diseases. We have found an accumulating evidence that indicates the MID1-PP2A complex plays a role in asthma and contributes to inflammation, but its roles in lung adenocarcinoma are unclear. This study aimed at evaluating the function of MID1-PP2A complex in human lung adenocarcinoma. METHODS: We used western blot, ELISA and real-time quantitative PCR to detect the protein and mRNA levels of MID1 and PP2A in A549, H1975, and H1650 lung adenocarcinoma cell lines compared with the human bronchial epithelial cell line BEAS-2B...
February 15, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29449555/intravenous-injections-of-the-oncolytic-virus-m1-as-a-novel-therapy-for-muscle-invasive-bladder-cancer
#14
Cheng Hu, Ying Liu, Yuan Lin, Jian-Kai Liang, Wen-Wen Zhong, Ke Li, Wen-Tao Huang, De-Juan Wang, Guang-Mei Yan, Wen-Bo Zhu, Jian-Guang Qiu, Xin Gao
Muscle-invasive bladder cancer (MIBC) is associated with low survival and high recurrence rates even in cases in which patients receive systemic treatments, such as surgery and chemotherapy. Here, we found that a naturally existing alphavirus, namely, M1, selectively kills bladder cancer cells but not normal cells, findings supported by our observations of changes in viral replication and MIBC and patient-derived MIBC cell apoptosis. Transcriptome analysis revealed that interferon-stimulated genes (ISGs) are expressed at low levels in sensitive bladder cancer cells and high levels in resistant cells...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449434/msh6-haploinsufficiency-at-relapse-contributes-to-the-development-of-thiopurine-resistance-in-pediatric-b-lymphoblastic-leukemia
#15
Nikki A Evensen, P Pallavi Madhusoodhan, Julia Meyer, Jason Saliba, Ashfiyah Chowdhury, David J Araten, Jacob Nersting, Teena Bhatla, Tiffaney L Vincent, David Teachey, Stephen P Hunger, Jun Yang, Kjeld Schmiegelow, William L Carroll
Survival of children with relapsed acute lymphoblastic leukemia is poor and understanding mechanisms underlying resistance is essential in developing new therapy. Relapse-specific heterozygous deletions in MSH6, a crucial part of DNA Mismatch Repair, are frequently detected. Our aim was to determine whether MSH6 deletion results in a hypermutator phenotype associated with generation of secondary mutations involved in drug resistance or leads to a failure to initiate apoptosis directly in response to chemotherapeutic agents...
February 15, 2018: Haematologica
https://www.readbyqxmd.com/read/29448633/copolymeric-micelles-loading-curcumin-preparation-characterization-and-in-vitro-evaluation
#16
Min Li, Li Lv, Aijie Guo, Yuanyuan Shen, Shengrong Guo
Curcumin (Cur) has potent antitumor activity; however, its clinical use is limited due to its hydrophobicity and instability at physiological pH. In this work, Cur was incorporated into MPEG2K-P(CL-co-LLA) micelles to form the Cur-loaded micelles with drug loadings from 4.72% to 35.21% depending on the ratios of drug to MPEG2K-P(CL-co-LLA). The resulting Cur-loaded micelles were spherical with mean hydrodynamic diameters in the range of 28.8 to 58.6 nm, having excellent water-solubility and good stability at pH 7...
March 1, 2018: Journal of Nanoscience and Nanotechnology
https://www.readbyqxmd.com/read/29448246/effect-of-mst1-on-endometriosis-apoptosis-and-migration-role-of-drp1-related-mitochondrial-fission-and-parkin-required-mitophagy
#17
Qingdong Zhao, Mingxia Ye, Wen Yang, Min Wang, Mingxia Li, Chenglei Gu, Luyang Zhao, Zhe Zhang, Weidong Han, Wensheng Fan, Yuanguang Meng
BACKGROUND/AIMS: Mitochondrial homeostasis is implicated in the development and progression of endometriosis through poorly defined mechanisms. Mst1 is the major growth suppressor related to cancer migration, apoptosis and proliferation. However, whether Mst1 is involved in endometriosis apoptosis and migration via regulating the mitochondrial function remains to be elucidated. METHODS: Expression of Mst1 in endometriosis was examined via western blots. Cellular apoptosis was detected via MTT and TUNEL assay...
February 9, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29448138/dual-targeting-antitumor-hybrids-derived-from-pt-iv-species-and-millepachine-analogues
#18
Xiaochao Huang, Shixian Hua, Rizhen Huang, Zhikun Liu, Shaohua Gou, Zhimei Wang, Zhixin Liao, Hengshan Wang
Many strategies have been developed to circumvent the shortcomings of Pt(II)-based chemotherapy, but the inherent problems still have not been effectively resolved. Here we report a new series of dual-targeting Pt(IV) prodrugs, conjugates of millepachine analogues with the related Pt(IV) complexes derived from cisplatin or oxaliplatin, respectively, which can inhibit tubulin polymerization and induce DNA damage. Among them, compound 19 possessed excellent antitumor activities against the tested human cancer cell lines, and arrested the cell cycle at the G2/M phases and ultimately induced cell apoptosis...
February 9, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29448055/proteomic-characterization-of-withaferin-a-targeted-protein-networks-for-the-treatment-of-monoclonal-myeloma-gammopathies
#19
Martin Dom, Fritz Offner, Wim Vanden Berghe, Xaveer Van Ostade
Withaferin A (WA), a natural steroid lactone from the plant Withania somnifera, is often studied because of its antitumor properties. Although many in vitro and in vivo studies have been performed, the identification of Withaferin A protein targets and its mechanism of antitumor action remain incomplete. We used quantitative chemoproteomics and differential protein expression analysis to characterize the WA antitumor effects on a multiple myeloma cell model. Identified relevant targets were further validated by Ingenuity Pathway Analysis and Western blot and indicate that WA targets protein networks that are specific for monoclonal gammopathy of undetermined significance (MGUS) and other closely related disorders, such as multiple myeloma (MM) and Waldenström macroglobulinemia (WM)...
February 12, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29447541/jtc-801-exerts-anti-proliferative-effects-in-human-osteosarcoma-cells-by-inducing-apoptosis
#20
Chang-Jun Zheng, Li-Li Yang, Jun Liu, Lei Zhong
BACKGROUND: The research of G protein-coupled receptors (GPCRs) is a promising strategy for drug discovery. In cancer therapy, there is a need to discover novel agents that can inhibit proliferation and induce apoptosis in cancer cells. JTC-801 is a novel GPCR antagonist with the function of reversing pain and anxiety symptoms. This study aims to investigate the antitumor effects of JTC-801 on human osteosarcoma cells (U2OS) and elucidate the underlying mechanism. MATERIALS AND METHODS: The Cell Counting Kit-8 assay was used to detect the viability of U2OS cells treated with JTC-801 in vitro...
February 15, 2018: Journal of Receptor and Signal Transduction Research
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