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https://www.readbyqxmd.com/read/29779163/discovering-simple-phenylboronic-acid-and-benzoxaborole-derivatives-for-experimental-oncology-phase-cycle-specific-inducers-of-apoptosis-in-a2780-ovarian-cancer-cells
#1
Mateusz Psurski, Agnieszka Łupicka-Słowik, Agnieszka Adamczyk-Woźniak, Joanna Wietrzyk, Andrzej Sporzyński
Objective The aim of the study was to evaluate the antiproliferative potential of simple phenylboronic acid and benzoxaborole derivatives as well as to provide preliminary insight into their mode of action in cancer cells in vitro. Methods The antiproliferative activity was assessed in five diverse cancer cell lines via the SRB method (sulforhodamine B) or MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method after 72 h of treatment. Further studies of the mechanism of action consisted of the influence of the compounds on cell cycle progression and apoptosis induction, which was assessed by flow cytometry, caspase-3 enzymatic activity, fluorescence microscopy and western blot analysis...
May 19, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29769406/spindle-assembly-disruption-and-cancer-cell-apoptosis-with-a-cltc-binding-compound
#2
Michael J Bond, Marina Bleiler, Lauren E Harrison, Eric W Scocchera, Masako Nakanishi, Narendran G-Dayanandan, Santosh Keshipeddy, Daniel W Rosenberg, Dennis L Wright, Charles Giardina
AK3 compounds are mitotic-arrest agents that induce high levels of γH2AX during mitosis and apoptosis following release from arrest. We synthesized a potent AK3 derivative, AK306, that induced arrest and apoptosis of the HCT116 colon cancer cell line with an EC50 of ~50 nM. AK306 was active on a broad spectrum of cancer cell lines with total growth inhibition values ranging from ~25 nM to 25 µM. Using biotin and BODIPY-linked derivatives of AK306, binding to clathrin heavy chain (CLTC/CHC) was observed, a protein with roles in endocytosis and mitosis...
May 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29750898/mebendazole-exhibits-potent-anti-leukemia-activity-on-acute-myeloid-leukemia
#3
Licai He, Liuzhi Shi, Zhuanyun Du, He Huang, Rui Gong, Lan Ma, Lianjuan Chen, Shenmeng Gao, Jianxin Lyu, Haihua Gu
Acute myeloid leukemia (AML) is one of the most common types of acute leukemia in adults with the lowest survival rate of all leukemia. Resistance to cytarabine and anthracycline-based chemotherapy is a major cause of treatment failure. Thus, finding new drugs with anti-leukemia activities and minimal side effect is urgently needed. Here through screening more than 1000 drugs approved by the Food and Drug Administration (FDA) of United States, the antihelmintic drug mebendazole (MBZ) was found to inhibit the growth of AML cell lines (THP-1, U937, NB4 and K562) and bone marrow mononuclear cells (BM-MNCs) from AML patients at pharmacologically achievable concentrations...
May 8, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29746542/depletion-of-mrna-export-regulator-dbp5-ddx19-gle1-or-ippk-that-is-a-key-enzyme-for-the-production-of-ip6-resulting-in-differentially-altered-cytoplasmic-mrna-expression-and-specific-cell-defect
#4
Masumi Okamura, Yasutaka Yamanaka, Maki Shigemoto, Yuya Kitadani, Yuhko Kobayashi, Taiho Kambe, Masaya Nagao, Issei Kobayashi, Katsuzumi Okumura, Seiji Masuda
DBP5, also known as DDX19, GLE1 and inositol hexakisphosphate (IP6) function in messenger RNA (mRNA) export at the cytoplasmic surface of the nuclear pore complex in eukaryotic cells. DBP5 is a DEAD-box RNA helicase, and its activity is stimulated by interactions with GLE1 and IP6. In addition, these three factors also have unique role(s). To investigate how these factors influenced the cytoplasmic mRNA expression and cell phenotype change, we performed RNA microarray analysis to detect the effect and function of DBP5, GLE1 and IP6 on the cytoplasmic mRNA expression...
2018: PloS One
https://www.readbyqxmd.com/read/29742018/the-kinase-domain-of-ck1-enzymes-contains-the-localization-cue-essential-for-compartmentalized-signaling-at-the-spindle-pole
#5
Zachary C Elmore, Rodrigo X Guillen, Kathleen L Gould
CK1 protein kinases contribute to multiple biological processes, but how they are tailored to function in compartmentalized signaling events is largely unknown. Hhp1 and Hhp2 (Hhp1/2) are the soluble CK1 family members in Schizosaccharomyces pombe. One of their functions is to inhibit the septation initiation network (SIN) during a mitotic checkpoint arrest. The SIN is assembled by Sid4 at spindle pole bodies (SPBs), and though Hhp1/2 co-localize there, it is not known how they are targeted there nor if their SPB localization is required for SIN inhibition...
May 9, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29739877/role-of-kip2-during-early-mitosis-impact-on-spindle-pole-body-separation-and-chromosome-capture
#6
Beryl Augustine, Cheen Fei Chin, Foong May Yeong
Mitotic spindle dynamics are regulated during the cell cycle by microtubule motor proteins. One such protein is Kip2p, a plus-ended motor that regulates the polymerization and stability of cytoplasmic microtubules (cMTs). Kip2p levels are regulated during the cell cycle and its overexpression leads to the formation of hyper-elongated cMTs. To investigate the significance of varying Kip2p levels during the cell cycle and the hyper-elongated cMTs, we overexpressed KIP2 in G1 phase and examined the effects on the separation of spindle pole bodies (SPBs) and chromosome segregation...
May 8, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29738338/growth-arrest-and-apoptosis-induced-by-kinesin-eg5-inhibitor-k858-and-by-its-1-3-4-thiadiazoline-analogue-in-tumor-cells
#7
Sabrina Giantulli, Francesca De Iuliis, Ludovica Taglieri, Simone Carradori, Giusi Menichelli, Stefania Morrone, Susanna Scarpa, Ida Silvestri
Tumors are complex and heterogeneous but, despite this, they share the ability to proliferate continuously, irrespective of the presence of growth signals, leading to a higher fraction of actively growing and dividing cells compared with normal tissues. For this reason, the cytotoxic antimitotic treatments remain an important clinical tool for tumors. Among these drugs, antitubulin compounds constitute one of the most effective anticancer chemotherapies; however, they cause dose-limiting side effects. Therefore, it is still necessary to develop compounds with new targets and new mechanisms of action to reduce side effects or chemoresistance...
May 5, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29735611/survivin-inhibitors-mitigate-chemotherapeutic-resistance-in-breast-cancer-cells-by-suppressing-genotoxic-nf-kappab-activation
#8
Wei Wang, Bo Zhang, Arul M Mani, Zhongzhi Wu, Yu Fan, Wei Li, Zhao-Hui Wu
Therapeutic resistance developed after chemotherapy and aggressive metastasis are the major causes for cancer-related death in triple negative breast cancer (TNBC) patients. Survivin is the smallest member of Inhibitor-of-Apoptosis Proteins (IAPs) family, which plays critical roles in cell division and cell survival. High expression levels of survivin have been associated with therapeutic resistance in various cancers. We recently developed a novel small molecule survivin inhibitor mimicking IAP-binding motif of second mitochondria-derived activator of caspase, which showed high potency in promoting survivin degradation...
May 7, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29719262/augmentation-of-myc-dependent-mitotic-gene-expression-by-the-pygopus2-chromatin-effector
#9
Phillip G P Andrews, Catherine Popadiuk, Thomas J Belbin, Kenneth R Kao
Mitotic segregation of chromosomes requires precise coordination of many factors, yet evidence is lacking as to how genes encoding these elements are transcriptionally controlled. Here, we found that the Pygopus (Pygo)2 chromatin effector is indispensable for expression of the MYC-dependent genes that regulate cancer cell division. Depletion of Pygo2 arrested SKOV-3 cells at metaphase, which resulted from the failure of chromosomes to capture spindle microtubules, a critical step for chromosomal biorientation and segregation...
May 1, 2018: Cell Reports
https://www.readbyqxmd.com/read/29713275/the-novel-small-molecule-stk899704-promotes-senescence-of-the-human-a549-nsclc-cells-by-inducing-dna-damage-responses-and-cell-cycle-arrest
#10
Chan-Woo Park, Yesol Bak, Min-Je Kim, Ganipisetti Srinivasrao, Joonsung Hwang, Nak K Sung, Bo Yeon Kim, Jae-Hyuk Yu, Jin Tae Hong, Do-Young Yoon
The novel synthetic compound designated STK899704 (PubChem CID: 5455708) suppresses the proliferation of a broad range of cancer cell types. However, the details of its effect on lung cancer cells are unclear. We investigated the precise anticancer effect of STK899704 on senescence and growth arrest of A549 human non-small cell lung cancer (NSCLC) cells. STK899704 affected NSCLC cell cycle progression and decreased cell viability in a dose-dependent manner. Immunofluorescence staining revealed that STK899704 destabilized microtubules...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29710496/dehydrocostus-lactone-induces-prominent-apoptosis-in-kidney-distal-tubular-epithelial-cells-and-interstitial-fibroblasts-along-with-cell-cycle-arrest-in-ovarian-epithelial-cells
#11
Soma Shiva Nageswara Rao Singireesu, Sujan Kumar Mondal, Sunil Misra, Suresh Yerramsetty, Suresh Babu K
Dehydrocostus lactone (DHCL), a sesquiterpene lactone is well-known for its antiulcer, anti-hepatotoxic and anticancer activity. However, the studies concerning the safety/toxicity potential of DHCL toward the cells of normal origin remain unclear. The present study is aimed at investigating the toxicity potential of DHCL in renal distal tubular and interstitial fibroblast cell lines (MDCK and NRK-49F cells, respectively), and also in ovarian epithelial cell line (CHO cells). The MTT assay has predicted potential cytotoxic activity of DHCL against the cell line types with IC50 values of 0...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29704982/cellular-senescence-in-postmitotic-cells-beyond-growth-arrest
#12
REVIEW
Przemyslaw Sapieha, Frédérick A Mallette
In mitotic cells, cellular senescence is a permanent state of G1 arrest, that may have evolved in parallel to apoptosis, to limit proliferation of damaged cells and oncogenesis. Recent studies have suggested that postmitotic cells are also capable of entering a state of senescence, although the repercussions of postmitotic cellular senescence (PoMiCS) on tissue health and function are currently ill-defined. In tissues made largely of post-mitotic cells, it is evolutionary advantageous to preserve cellular integrity and cellular senescence of post-mitotic cells may prevent stressor-induced tissue degeneration and promote tissue repair...
April 25, 2018: Trends in Cell Biology
https://www.readbyqxmd.com/read/29700288/atp-depletion-during-mitotic-arrest-induces-mitotic-slippage-and-apc-c-cdh1-dependent-cyclin-b1-degradation
#13
Yun Yeon Park, Ju-Hyun Ahn, Min-Guk Cho, Jae-Ho Lee
ATP depletion inhibits cell cycle progression, especially during the G1 phase and the G2 to M transition. However, the effect of ATP depletion on mitotic progression remains unclear. We observed that the reduction of ATP after prometaphase by simultaneous treatment with 2-deoxyglucose and NaN3 did not arrest mitotic progression. Interestingly, ATP depletion during nocodazole-induced prometaphase arrest resulted in mitotic slippage, as indicated by a reduction in mitotic cells, APC/C-dependent degradation of cyclin B1, increased cell attachment, and increased nuclear membrane reassembly...
April 27, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29689351/the-fruits-of-gleditsia-sinensis-lam-inhibits-adipogenesis-through-modulation-of-mitotic-clonal-expansion-and-stat3-activation-in-3t3-l1-cells
#14
Ji-Hye Lee, Younghoon Go, Bonggi Lee, Youn-Hwan Hwang, Kwang Il Park, Won-Kyung Cho, Jin Yeul Ma
ETHNOPHARMACOLOGICAL RELEVANCE: Gleditsia sinensis Lam. (G. sinensis) has been used in Oriental medicine for tumor, thrombosis, inflammation-related disease, and obesity. AIM OF THE STUDY: The pharmacological inhibitory effects of fruits of G. sinensis (GFE) on hyperlipidemia have been reported, but its inhibitory effects on adipogenesis and underlying mechanisms have not been elucidated. Herein we evaluated the anti-adipogenic effects of GFE and described the underlying mechanisms...
April 21, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29688323/silac-based-phosphoproteomics-reveals-new-pp2a-cdc55-regulated-processes-in-budding-yeast
#15
Barbara Baro, Soraya Játiva, Inés Calabria, Judith Vinaixa, Joan-Josep Bech-Serra, Carolina de LaTorre, João Rodrigues, María Luisa Hernáez, Concha Gil, Silvia Barceló-Batllori, Martin R Larsen, Ethel Queralt
Background: Protein phosphatase 2A (PP2A) is a family of conserved serine/threonine phosphatases involved in several essential aspects of cell growth and proliferation. PP2ACdc55 phosphatase has been extensively related to cell cycle events in budding yeast, however few PP2ACdc55 substrates have been identified. Here, we performed a quantitative mass spectrometry approach to reveal new substrates of PP2ACdc55 phosphatase and new PP2A-related processes in mitotic arrested cells. Results: We identified 62 statistically significant PP2ACdc55 substrates involved mainly in actin-cytoskeleton organization...
April 24, 2018: GigaScience
https://www.readbyqxmd.com/read/29679654/the-vanillin-derivative-6-bromine-5-hydroxy-4-methoxybenzaldehyde-induces-aberrant-mitotic-progression-and-enhances-radio-sensitivity-accompanying-suppression-the-expression-of-plk1-in-esophageal-squamous-cell-carcinoma
#16
Meng-Meng Gu, Ming Li, Dexuan Gao, Lang-Huan Liu, Yue Lang, Si-Ming Yang, Hongling Ou, Bo Huang, Ping-Kun Zhou, Zeng-Fu Shang
Esophageal squamous cell carcinoma (ESCC) is the most common form of esophageal cancer in China. Since chemotherapy is the standard clinical intervention for advanced ESCC, the development of highly effective and minimal/non-toxic drugs is essential to improve the clinical outcome and prognosis of the patients. A novel derivative of vanillin, 6-bromine-5-hydroxy-4-methoxybenzaldehyde (BVAN08), has been recently reported to activate different cell death pathways in cancer cells. In this study, we demonstrate that BVAN08 exhibits a potent anti-proliferation effect on ESCC cells (TE-1 and ECA-109) by inhibiting the expression of PLK1, an important mitotic kinase...
April 18, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29674690/ultrasound-activated-piezoelectric-nanoparticles-inhibit-proliferation-of-breast-cancer-cells
#17
Attilio Marino, Matteo Battaglini, Daniele De Pasquale, Andrea Degl'Innocenti, Gianni Ciofani
A nanotechnology-based approach for the inhibition of breast cancer cell proliferation is proposed. The innovative solution consists in a platform based on biocompatible piezoelectric nanoparticles able to target and remotely stimulate HER2-positive breast cancer cells. The anti-proliferative effects of the ultrasound-driven piezoelectric nanoparticle-assisted stimulation significantly reduced the proliferation by inducing the cell cycle arrest. Similarly to a low-intensity alternating electric field, chronic piezoelectric stimulation resulted able to inhibit cancer cell proliferation by upregulating the expression of the gene encoding Kir3...
April 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29672918/ionizing-radiation-but-not-ultraviolet-radiation-induces-mitotic-catastrophe-in-mouse-epidermal-keratinocytes-with-aberrant-cell-cycle-checkpoints
#18
Ming Wang, QingXiang Gao, Xu Teng, MeiPing Pan, TianMiao Lin, GuiXuan Zhou, BenHua Xu, ZhiCao Yue
Ultraviolet radiation (UVR) and ionizing radiation (IR) are common genotoxic stresses that damage human skin, although the specific damages to the genomic DNA are different. Here we show that in the mouse glabrous skin, both UVR and IR induce DNA damage, cell cycle arrest, and condensed cell nuclei. However, only IR induces mitotic catastrophe (MC) in the epidermis. This is because UVR induces a complete blockage of pRB phosphorylation and cell cycle arrest in the G1 phase, whereas pRB phosphorylation remains positive in a significant portion of the epidermal keratinocytes following IR exposure...
April 19, 2018: Experimental Dermatology
https://www.readbyqxmd.com/read/29663555/dehydroleucodine-inhibits-mitotic-clonal-expansion-during-adipogenesis-through-cell-cycle-arrest
#19
S Abood, M L Veisaga, L A López, M A Barbieri
Aberrant levels of preadipocyte differentiation, triggered by adipocyte hyperplasia and hypertrophy, results in the obesogenic phenotype. Obesity is a risk factor for several metabolic disorders. In this paper, dehydroleucodine inhibited the accumulation of lipid droplets and decreased the elevations of triglycerides, and this inhibitory effect occurred during the early stage of adipogenesis. Thus, not only did dehydroleucodine downregulate the expression of C/EBPα and PPARγ, it also strongly blocked the expression of C/EBPβ, an early stage biomarker of early adipogenesis, in a concentration-dependent manner...
April 16, 2018: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29658881/negative-regulation-of-g2-m-by-atr-mei-41-chk1-grapes-facilitates-tracheoblast-growth-and-tracheal-hypertrophy-in-drosophila
#20
Amrutha Kizhedathu, Archit V Bagul, Arjun Guha
Imaginal progenitors in Drosophila are known to arrest in G2 during larval stages and proliferate thereafter. Here we investigate the mechanism and implications of G2 arrest in progenitors of the adult thoracic tracheal epithelium (tracheoblasts). We report that tracheoblasts pause in G2 for ~48-56 h and grow in size over this period. Surprisingly, tracheoblasts arrested in G2 express drivers of G2-M like Cdc25/String (Stg). We find that mechanisms that prevent G2-M are also in place in this interval. Tracheoblasts activate Checkpoint Kinase 1/Grapes (Chk1/Grp) in an ATR/mei-41-dependent manner...
April 16, 2018: ELife
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