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https://www.readbyqxmd.com/read/27922047/new-arylated-benzo-h-quinolines-induce-anti-cancer-activity-by-oxidative-stress-mediated-dna-damage
#1
Dharmendra K Yadav, Reeta Rai, Naresh Kumar, Surjeet Singh, Sanjeev Misra, Praveen Sharma, Priyanka Shaw, Horacio Pérez-Sánchez, Ricardo L Mancera, Eun Ha Choi, Mi-Hyun Kim, Ramendra Pratap
The anti-cancer activity of the benzo[h]quinolines was evaluated on cultured human skin cancer (G361), lung cancer (H460), breast cancer (MCF7) and colon cancer (HCT116) cell lines. The inhibitory effect of these compounds on the cell growth was determined by the MTT assay. The compounds 3e, 3f, 3h and 3j showed potential cytotoxicity against these human cancer cell lines. Effect of active compounds on DNA oxidation and expression of apoptosis related gene was studied. We also developed a quantitative method to measure the activity of cyclin-dependent kinases-2 (CDK2) by western blotting in the presence of active compound...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27909065/cdk5-directly-targets-nuclear-p21cip1-and-promotes-cancer-cell-growth
#2
Pao-Hsuan Huang, Mei-Chih Chen, Yu-Ting Peng, Wei-Hsiang Kao, Chih-Hsiang Chang, Yun-Chi Wang, Chih-Ho Lai, Jer-Tsong Hsieh, Jo-Hsin Wang, Yueh-Tsung Lee, Eugene Lin, Chia-Herng Yue, Hsin-Yi Wang, Shuen-Chi You, Ho Lin
The significance of Cdk5 in cell-cycle control and cancer biology has gained increased attention. Here we report the inverse correlation between the protein levels of Cdk5 and p21(CIP1) from cell-based and clinical analysis. Mechanistically, we identify that Cdk5 overexpression triggers the proteasome-dependent degradation of p21(CIP1) through a S130 phosphorylation in a Cdk2-independent manner. Besides, the evidence from cell-based and clinical analysis shows that Cdk5 primarily regulates nuclear p21(CIP1) protein degradation...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27904776/microrna-195-suppresses-colorectal-cancer-cells-proliferation-via-targeting-fgf2-and-regulating-wnt-%C3%AE-catenin-pathway
#3
Xianxiang Zhang, Ji Xu, Tao Jiang, Guangwei Liu, Dongsheng Wang, Yun Lu
Colorectal cancer (CRC) is a prevalent cancer with high mortality worldwide. This study was aimed to explore the functional effects of microRNA-195 (miR-195) on CRC cells and the underling mechanism involved. quantitative PCR (qPCR) was performed to monitor the expression of miR-195 in CRC tissues and cell lines. SW480 and SW620 cells were transfected with either miR-195 mimic or antisense oligonucleotides (ASO) of miR-195. Then cell viability, cell cycle and the expressions of CyclinB1, CyclinD1 and Cyclin-Dependent Kinase 2 (CDK2) were respectively detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyltetrazolium bromide (MTT), flow cytometry, qPCR and Western blot...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27903987/mapping-heterogeneity-in-patient-derived-melanoma-cultures-by-single-cell-rna-seq
#4
Tobias Gerber, Edith Willscher, Henry Loeffler-Wirth, Lydia Hopp, Dirk Schadendorf, Manfred Schartl, Ulf Anderegg, Gray Camp, Barbara Treutlein, Hans Binder, Manfred Kunz
Recent technological advances in single-cell genomics make it possible to analyze cellular heterogeneity of tumor samples. Here, we applied single-cell RNA-seq to measure the transcriptomes of 307 single cells cultured from three biopsies of three different patients with a BRAF/NRAS wild type, BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant melanoma metastasis, respectively. Analysis based on self-organizing maps identified sub-populations defined by multiple gene expression modules involved in proliferation, oxidative phosphorylation, pigmentation and cellular stroma...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899159/p53-signaling-modulation-of-cell-cycle-arrest-and-viral-replication-in-porcine-circovirus-type-2-infection-cells
#5
Dan Xu, Qian Du, Cong Han, Zengguo Wang, Xiujuan Zhang, Tongtong Wang, Xiaomin Zhao, Yong Huang, Dewen Tong
Porcine circovirus type 2 (PCV2) is a ubiquitous pathogen in the swine industry worldwide. Previous studies have shown that PCV2 infection induces host cell apoptosis through up-regulation of p53. To further identify the regulatory roles of p53 signaling in the process of PCV2 infection, we established p53 gene knockout PK15 cell lines using the genomic editor tool CRISPR/Cas9, and further investigated the roles of p53 in modulating the cell cycle and viral replication in this study. The results show that PCV2 infection induced obvious S phase accumulation in wild-type PK15 cells and a compromised S phase accumulation in the p53 gene mutation cells (813PK15 (p53m/m) ), but did not induce obvious S phase accumulation in the p53 gene knockout cells (148PK15 (p53-/-)) compared with the respective mock infection...
November 29, 2016: Veterinary Research
https://www.readbyqxmd.com/read/27898692/targeting-cdks-with-roscovitine-increases-sensitivity-to-dna-damaging-drugs-of-human-osteosarcoma-cells
#6
Serena Vella, Elisa Tavanti, Claudia Maria Hattinger, Marilù Fanelli, Rogier Versteeg, Jan Koster, Piero Picci, Massimo Serra
Cyclin-dependent kinase 2 (CDK2) has been reported to be essential for cell proliferation in several human tumours and it has been suggested as an appropriate target to be considered in order to enhance the efficacy of treatment regimens based on the use of DNA damaging drugs. We evaluated the clinical impact of CDK2 overexpression on a series of 21 high-grade osteosarcoma (OS) samples profiled by using cDNA microarrays. We also assessed the in vitro efficacy of the CDKs inhibitor roscovitine in a panel of drug-sensitive and drug-resistant human OS cell lines...
2016: PloS One
https://www.readbyqxmd.com/read/27895463/lentivirus-mediated-knockdown-of-nlk-inhibits-small-cell-lung-cancer-growth-and-metastasis
#7
Mutian Lv, Yaming Li, Xin Tian, Shundong Dai, Jing Sun, Guojiang Jin, Shenyi Jiang
Nemo-like kinase (NLK), an evolutionarily conserved serine/threonine kinase, has been recognized as a critical regulator of various cancers. In this study, we investigated the role of NLK in human small-cell lung cancer (SCLC), which is the most aggressive form of lung cancer. NLK expression was evaluated by quantitative real-time polymerase chain reaction in 20 paired fresh SCLC tissue samples and found to be noticeably elevated in tumor tissues. Lentivirus-mediated RNAi efficiently suppressed NLK expression in NCI-H446 cells, resulting in a significant reduction in cell viability and proliferation in vitro...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27890856/sirna-cell-penetrating-peptides-complexes-as-a-combinatorial-therapy-against-chronic-myeloid-leukemia-using-bv173-cell-line-as-model
#8
João Miguel Freire, Inês Rego de Figueiredo, Javier Valle, Ana Salomé Veiga, David Andreu, Francisco J Enguita, Miguel A R B Castanho
Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by a single gene mutation, a reciprocal translocation that originates the Bcr-Abl gene with constitutive tyrosine kinase activity. As a monogenic disease, it is an optimum target for RNA silencing therapy. We developed a siRNA-based therapeutic approach in which the siRNA is delivered by pepM or pepR, two cell-penetrating peptides (CPPs) derived from the dengue virus capsid protein. These peptides have a dual role: siRNA delivery into cells and direct action as bioportides, i...
November 24, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27888798/mir-103-inhibits-proliferation-and-sensitizes-hemopoietic-tumor-cells-for-glucocorticoid-induced-apoptosis
#9
Shlomit Kfir-Erenfeld, Noa Haggiag, Moshe Biton, Polina Stepensky, Nathalie Assayag-Asherie, Eitan Yefenof
Glucocorticoid (GC) hormones are an important ingredient of leukemia therapy since they are potent inducers of lymphoid cell apoptosis. However, the development of GC resistance remains an obstacle in GC-based treatment. In the present investigation we found that miR-103 is upregulated in GC-sensitive leukemia cells treated by the hormone. Transfection of GC resistant cells with miR-103 sensitized them to GC induced apoptosis (GCIA), while miR-103 sponging of GC sensitive cells rendered them partially resistant...
November 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27882217/multiple-effects-of-xihuang-pill-aqueous-extract-on-the-hs578t-triple-negative-breast-cancer-cell-line
#10
Wenxian Zheng, Shuyan Han, Shantong Jiang, Lina Pang, Xiaohong Li, Xijuan Liu, Minhua Cao, Pingping Li
The management of triple-negative breast cancer (TNBC) is challenging due to the aggressive behavior, lack of therapeutic options and relatively poor prognosis. Xihuang pill (XHP) is a well-known Traditional Chinese Medicine with anticancer activity. The aim of the present study was to investigate whether the aqueous extract of XHP (AEXHP) has anti-proliferative activity against the Hs578T TNBC cell line, and to elucidate its molecular mechanisms of action. First, an MTT assay was used to evaluate the anti-proliferative activity of AEXHP on the Hs578T cell line; furthermore, the cell cycle distribution, mitochondrial membrane potential and apoptotic rate were determined by flow cytometry, and western blot analysis was used to assess the expression of apoptosis and cell cycle regulatory proteins to investigate the mechanisms of action...
November 2016: Biomedical Reports
https://www.readbyqxmd.com/read/27872619/ebola-vp40-in-exosomes-can-cause-immune-cell-dysfunction
#11
Michelle L Pleet, Allison Mathiesen, Catherine DeMarino, Yao A Akpamagbo, Robert A Barclay, Angela Schwab, Sergey Iordanskiy, Gavin C Sampey, Benjamin Lepene, Sergei Nekhai, M J Aman, Fatah Kashanchi
Ebola virus (EBOV) is an enveloped, ssRNA virus from the family Filoviridae capable of causing severe hemorrhagic fever with up to 80-90% mortality rates. The most recent outbreak of EBOV in West Africa starting in 2014 resulted in over 11,300 deaths; however, long-lasting persistence and recurrence in survivors has been documented, potentially leading to further transmission of the virus. We have previously shown that exosomes from cells infected with HIV-1, HTLV-1 and Rift Valley Fever virus are able to transfer viral proteins and non-coding RNAs to naïve recipient cells, resulting in an altered cellular activity...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27864121/gene-amplification-of-ccne1-ccnd1-and-cdk6-in-gastric-cancers-detected-by-multiplex-ligation-dependent-probe-amplification-and-fluorescence-in-situ-hybridization
#12
Akishi Ooi, Takeru Oyama, Ritsuko Nakamura, Ryousuke Tajiri, Hiroko Ikeda, Sachio Fushida, Yoh Dobashi
New and effective treatments for advanced gastric cancer are urgently needed. Cyclins E and D1 form a complex with cyclin-dependent kinase 2 (CDK2), 4 or 6 to regulate G1-S transition. The G1-S regulatory genes encoding cyclin E (CCNE1), cyclin D1 (CCND1) and CDK6 (CDK6) are frequently amplified in gastric cancer and may therefore influence molecularly targeted therapies against ERBB2 or EGFR when co-amplified. A total of 179 formalin-fixed and paraffin-embedded gastric cancer specimens were examined for these gene amplifications by multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridization (FISH)...
November 15, 2016: Human Pathology
https://www.readbyqxmd.com/read/27863310/cyclin-dependent-kinase-2-promotes-tumor-proliferation-and-induces-radio-resistance-in-glioblastoma
#13
Jia Wang, Tong Yang, Gaofeng Xu, Hao Liu, Chunying Ren, Wanfu Xie, Maode Wang
Accumulating evidence indicates that CDK2 promotes hyperproliferation and is associated to poor prognosis in multiple cancer cells. However, the physiological role of CDK2 in GBM and the biological mechanism still remains unclear. In this study, we identified that CDK2 expression was significantly enriched in GBM tumors compared with normal brain. Additionally, CDK2 was functionally required for tumor proliferation and its expression was associated to poor prognosis in GBM patients. Mechanically, CDK2 induced radio resistance in GBM cells and CDK2 knock down increased cell apoptosis when combined with radiotherapy...
November 15, 2016: Translational Oncology
https://www.readbyqxmd.com/read/27863047/theoretical-studies-on-the-selective-mechanisms-of-gsk3%C3%AE-and-cdk2-by-molecular-dynamics-simulations-and-free-energy-calculations
#14
Sufang Zhao, Jingyu Zhu, Lei Xu, Jian Jin
Glycogen synthase kinase 3 (GSK3) is a serine/threonine protein kinase which is widely involved in cell signaling and controls a broad number of cellular functions. GSK3 contains α and β isoforms, and GSK3β has received more attention and becomes an attractive drug target for the treatment of several diseases. The binding pocket of Cyclin-dependent kinases 2 (CDK2) shares high sequence identity to that of GSK3β, and therefore the design of highly selective inhibitors towards GSK3β remains a big challenge...
November 11, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27862183/the-antiviral-cytokine-interferon-gamma-restricts-neural-stem-progenitor-cell-proliferation-through-activation-of-stat1-and-modulation-of-retinoblastoma-protein-phosphorylation
#15
Apurva Kulkarni, Taylor J Scully, Lauren A O'Donnell
Neural stem/progenitor cells (NPSCs) express receptors for many inflammatory cytokines, with varying effects on differentiation and proliferation depending on the stage of development and the milieu of inflammatory mediators. In primary neurons and astrocytes, we recently showed that interferon gamma (IFNγ), a potent antiviral cytokine that is required for the control and clearance of many central nervous system (CNS) infections, could differentially affect cell survival and cell cycle progression depending upon the cell type and the profile of activated intracellular signaling molecules...
November 15, 2016: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27860401/probing-an-allosteric-pocket-of-cdk2-with-small-molecules
#16
Michael S Christodoulou, Fabiana Caporuscio, Valentina Restelli, Luca Carlino, Giuseppe Cannazza, Elisa Costanzi, Cinzia Citti, Leonardo Lo Presti, Pasquale Pisani, Roberto Battistutta, Massimo Broggini, Daniele Passarella, Giulio Rastelli
The availability of well characterized allosteric modulators is of crucial importance for investigating allosteric regulation of protein function. In a recently identified inactive conformation of CDK2 an open allosteric pocket has been detected and proposed as a site to accommodate allosteric inhibitors. Previous structure-based approaches allowed the identification of a hit compound expected to bind to this pocket. Here, we report the characterization of this compound by X-ray crystallography, which surprisingly provided a chemical structure different from the one previously reported...
November 18, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27855372/small-molecule-th-39-potentially-targets-hec1-nek2-interaction-and-exhibits-antitumor-efficacy-in-k562-cells-via-g0-g1-cell-cycle-arrest-and-apoptosis-induction
#17
Yongxia Zhu, Wei Wei, Tinghong Ye, Zhihao Liu, Li Liu, Yong Luo, Lidan Zhang, Chao Gao, Ningyu Wang, Luoting Yu
BACKGROUND: Cancer is still a major public health issue worldwide, and new therapeutics with anti-tumor activity are still urgently needed. METHODS: The anti-tumor activity of TH-39, which shows potent anti-proliferative activity against K562 cells with an IC50 of 0.78 µM, was investigated using immunoblot, co-immunoprecipitation, the MTT assay, and flow cytometry. RESULTS: Mechanistically, TH-39 may disrupt the interaction between Hec1 and Nek2 in K562 cells...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27849335/mycotoxin-verrucarin-a-inhibits-proliferation-and-induces-apoptosis-in-prostate-cancer-cells-by-inhibiting-prosurvival-akt-nf-kb-mtor-signaling
#18
Yongbo Liu, Xiaohua Gao, Dorrah Deeb, Yiguan Zhang, Jiajiu Shaw, Frederick A Valeriote, Subhash C Gautam
Trichothecenes are powerful mycotoxins that inhibit protein synthesis and induce ribotoxic stress response in mammalian cells. Verrucarin A (VC-A) is a Type D macrocyclic mycotoxin which inhibits cell proliferation and induces apoptosis in cancer cells. However, the antitumor activity of VC-A for prostate cancer cells has not been investigated. The objective of the present study was to determine the anticancer activity and its mechanism of action in hormone-responsive (LNCaP) and hormone-refractory (PC-3) carcinoma of the prostate (CaP) cell lines...
November 2016: Journal of Experimental Therapeutics & Oncology
https://www.readbyqxmd.com/read/27835685/light-tnfsf14-increases-the-survival-and-proliferation-of-human-bone-marrow-derived-mesenchymal-stem-cells
#19
Sook-Kyoung Heo, Eui-Kyu Noh, Gi-Dong Gwon, Jeong Yi Kim, Jae-Cheol Jo, Yunsuk Choi, SuJin Koh, Jin Ho Baek, Young Joo Min, Hawk Kim
LIGHT (HVEM-L, TNFSF14, or CD258), an entity homologous to lymphotoxins, with inducible nature and the ability to compete with herpes simplex virus glycoprotein D for herpes virus entry mediator (HVEM)/tumor necrosis factor (TNF)-related 2, is a member of the TNF superfamily. It is expressed as a homotrimer on activated T cells and dendritic cells (DCs), and has three receptors: HVEM, LT-β receptor (LTβR), and decoy receptor 3 (DcR3). So far, three receptors with distinct cellular expression patterns are known to interact with LIGHT...
2016: PloS One
https://www.readbyqxmd.com/read/27834307/effects-of-tanshinone-nanoemulsion-and-extract-on-inhibition-of-lung-cancer-cells-a549
#20
W D Lee, Y J Liang, B H Chen
Danshen (Salvia miltiorrhiza), a Chinese medicinal herb, consists of several functional components including tanshinones responsible for prevention of several chronic diseases. This study intends to prepare tanshinone extract and nanoemulsion from danshen and determine their inhibition effect on lung cancer cells A549. A highly stable tanshinone nanoemulsion composed of Capryol 90, Tween 80, ethanol and deionized water with the mean particle size of 14.2 nm was successfully prepared. Tanshinone nanoemulsion was found to be more effective in inhibiting A549 proliferation than tanshinone extract...
December 9, 2016: Nanotechnology
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