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https://www.readbyqxmd.com/read/28320095/dt-13-a-saponin-monomer-13-of-the-dwarf-lilyturf-tuber-synergized-with-vinorelbine-to-induce-mitotic-arrest-via-activation-of-erk-signaling-pathway-in-nci-h1299-cells
#1
Hongyang Li, Li Sun, Hang Li, Xiaodan Lv, Herve Semukunzi, Ruiming Li, Jun Yu, Shengtao Yuan, Sensen Lin
Vinorelbine (NVB) is a semi-synthetic vinca alkaloid that is approved for the clinical therapy of lung cancer. However, the clinical application of NVB was limited because of the acquisition of resistance and inacceptable toxicity. Therefore, it is of great interest to develop low-cytotoxic drugs that can synergize with NVB. DT-13, a saponin monomer 13 of the Dwarf lilyturf tuber, showed inhibitory effects on tumor metastasis and angiogenesis in the previous studies. Here, we found that DT-13 combined with NVB exhibited synergistic effect to inhibit the cell proliferation in human lung cancer NCI-H1299 cells rather than human embryonic lung fibroblasts WI-38...
March 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28319828/genistein-affects-proliferation-and-migration-of-bovine-oviductal-epithelial-cells
#2
Daniela C García, Pablo A Valdecantos, Dora C Miceli, Mariela Roldán-Olarte
Genistein is one of the most abundant isoflavones in soybean. This molecule induces cell cycle arrest and apoptosis in different normal and cancer cells. Genistein has been of considerable interest due to its adverse effects on bovine reproduction, altering estrous cycle, implantation and fetal development and producing subfertility or infertility. The objective of this work was to study the effects of genistein on the expression of selected genes involved in the regulation of cell cycle and apoptosis. Primary cultures of bovine oviductal epithelial cells (BOEC) were treated with different genistein concentrations (0...
March 8, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28315973/stem-cell-factor-kit-signal-insufficiency-contributes-to-hypoxia-induced-intestinal-motility-dysfunctions-in-neonatal-mice
#3
Hong Ren, Juan Han, Zhifang Li, Zhiyong Xiong
BACKGROUND: Gastrointestinal (GI) motility disorders represent a group of problems that more constantly encountered in preterm infants. However, whether hypoxia exposure contributes to the GI dysfunctions is still unclear. METHODS: Newborn mice were exposed to hypoxia (10%) from P1 to P7. Intestinal motilities were examined by a strain gauge transducer. The proliferation of ICCs was detected by using immunostaining for BrdU, Ki67, Kit, Ano1, and insulin-like growth factor 1 receptor (IGF-1R+)...
March 18, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28315713/maternal-senp7-programs-meiosis-architecture-and-embryo-survival-in-mouse
#4
ChunJie Huang, Di Wu, XiaoFei Jiao, Faheem Ahmed Khan, ChengLiang Xiong, XiaoMing Liu, Jing Yang, TaiLang Yin, LiJun Huo
Understanding the mechanisms underlying abnormal egg production and pregnancy loss is significant for human fertility. SENP7, a SUMO poly-chain editing enzyme, has been regarded as a mitotic regulator of heterochromatin integrity and DNA repair. Herein, we report the roles of SENP7 in mammalian reproductive scenario. Mouse oocytes deficient in SENP7 experienced meiotic arrest at prophase I and metaphase I stages, causing substantial decrease of mature eggs. Hyperaceylation and hypomethylation of histone H3 and up-regulation of Cdc14B/C accompanied by down-regulation of CyclinB1 and CyclinB2 were further recognized as contributors to defective M-phase entry and spindle assembly in oocytes...
March 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28315405/location-and-functional-analysis-of-the-aspergillus-nidulans-aurora-kinase-confirm-mitotic-functions-and-suggest-non-mitotic-roles
#5
Colin P De Souza, Shahr B Hashmi, Natalie Hage, Rebecca M Fitch, Aysha H Osmani, Stephen A Osmani
Filamentous fungi have devastating negative impacts as pathogens and agents of food spoilage but also have critical ecological importance and are utilized for industrial applications. The characteristic multinucleate nature of filamentous fungi is facilitated by limiting if, when and where septation, the fungal equivalent of cytokinesis, occurs. In the model filamentous fungus Aspergillus nidulans septation does not occur immediately after mitosis and is an incomplete process resulting in the formation of a septal pore whose permeability is cell cycle regulated...
March 14, 2017: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/28314740/dual-recognition-of-chromatin-and-microtubules-by-incenp-is-important-for-mitotic-progression
#6
Michael S Wheelock, David J Wynne, Boo Shan Tseng, Hironori Funabiki
The chromosomal passenger complex (CPC), composed of inner centromere protein (INCENP), Survivin, Borealin, and the kinase Aurora B, contributes to the activation of the mitotic checkpoint. The regulation of CPC function remains unclear. Here, we reveal that in addition to Survivin and Borealin, the single α-helix (SAH) domain of INCENP supports CPC localization to chromatin and the mitotic checkpoint. The INCENP SAH domain also mediates INCENP's microtubule binding, which is negatively regulated by Cyclin-dependent kinase-mediated phosphorylation of segments flanking the SAH domain...
March 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28298492/-wait-anaphase-signals-are-not-confined-to-the-mitotic-spindle
#7
Lydia Reńe Heasley, Steven M Markus, Jennifer G DeLuca
The Spindle Assembly Checkpoint ensures the faithful inheritance of chromosomes by arresting mitotic progression in the presence of kinetochores that are not attached to spindle microtubules. This is achieved through inhibition of the Anaphase Promoting Complex/Cyclosome by a kinetochore-derived 'wait anaphase' signal known as the Mitotic Checkpoint Complex. It remains unclear whether the localization and activity of these inhibitory complexes are restricted to the mitotic spindle compartment or are diffusible throughout the cytoplasm...
March 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28296906/anticancer-activity-of-a-novel-small-molecule-tubulin-inhibitor-stk899704
#8
Krisada Sakchaisri, Sun-Ok Kim, Joonsung Hwang, Nak Kyun Soung, Kyung Ho Lee, Tae Woong Choi, Yongjun Lee, Chan-Mi Park, Naraganahalli R Thimmegowda, Phil Young Lee, Bettaswamigowda Shwetha, Ganipisetti Srinivasrao, Thi Thu Huong Pham, Jae-Hyuk Jang, Hye-Won Yum, Young-Joon Surh, Kyung S Lee, Hwangseo Park, Seung Jun Kim, Yong Tae Kwon, Jong Seog Ahn, Bo Yeon Kim
We have identified the small molecule STK899704 as a structurally novel tubulin inhibitor. STK899704 suppressed the proliferation of cancer cell lines from various origins with IC50 values ranging from 0.2 to 1.0 μM. STK899704 prevented the polymerization of purified tubulin in vitro and also depolymerized microtubule in cultured cells leading to mitotic arrest, associated with increased Cdc25C phosphorylation and the accumulation of both cyclin B1 and polo-like kinase 1 (Plk1), and apoptosis. Unlike many anticancer drugs such as Taxol and doxorubicin, STK899704 effectively displayed antiproliferative activity against multidrug-resistant cancer cell lines...
2017: PloS One
https://www.readbyqxmd.com/read/28294156/stk16-regulates-actin-dynamics-to-control-golgi-organization-and-cell-cycle
#9
Juanjuan Liu, Xingxing Yang, Binhua Li, Junjun Wang, Wenchao Wang, Jing Liu, Qingsong Liu, Xin Zhang
STK16 is a ubiquitously expressed, myristoylated, and palmitoylated serine/threonine protein kinase with underexplored functions. Recently, it was shown to be involved in cell division but the mechanism remains unclear. Here we found that human STK16 localizes to the Golgi complex throughout the cell cycle and plays important roles in Golgi structure regulation. STK16 knockdown or kinase inhibition disrupts actin polymers and causes fragmented Golgi in cells. In vitro assays show that STK16 directly binds to actin and regulates actin dynamics in a concentration- and kinase activity-dependent way...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28288624/cdk5-links-with-dna-damage-response-and-cancer
#10
REVIEW
Wan Liu, Jun Li, Yu-Shu Song, Yue Li, Yu-Hong Jia, Hai-Dong Zhao
As an atypical member of cyclin dependent kinase family, Cyclin dependent kinase 5 (Cdk5) is considered as a neuron-specific kinase in the past decade due to the abundant existence of its activator p35 in post-mitotic neurons. Recent studies show that Cdk5 participates in a series of biological and pathological processes in non-neuronal cells, and is generally dysregulated in various cancer cells. The inhibition or knockdown of Cdk5 has been proven to play an anti-cancer role through various mechanisms, and can synergize the killing effect of chemotherapeutics...
March 14, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28287508/live-imaging-to-study-microtubule-dynamic-instability-in-taxane-resistant-breast-cancers
#11
Richard Wang, Harris Wang, Zhixiang Wang
Taxanes such as docetaxel belong to a group of microtubule-targeting agents (MTAs) that are commonly relied upon to treat cancer. However, taxane resistance in cancerous cells drastically reduces the effectiveness of the drugs' long-term usage. Accumulated evidence suggests that the mechanisms underlying taxane resistance include both general mechanisms, such as the development of multidrug resistance due to the overexpression of drug-efflux proteins, and taxane-specific mechanisms, such as those that involve microtubule dynamics...
February 20, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28272472/disruptions-in-asymmetric-centrosome-inheritance-and-wdr62-aurora-kinase-b-interactions-in-primary-microcephaly
#12
Paraskevi Sgourdou, Ketu Mishra-Gorur, Ichiko Saotome, Octavian Henagariu, Beyhan Tuysuz, Cynthia Campos, Keiko Ishigame, Krinio Giannikou, Jennifer L Quon, Nenad Sestan, Ahmet O Caglayan, Murat Gunel, Angeliki Louvi
Recessive mutations in WD repeat domain 62 (WDR62) cause microcephaly and a wide spectrum of severe brain malformations. Disruption of the mouse ortholog results in microcephaly underlain by reduced proliferation of neocortical progenitors during late neurogenesis, abnormalities in asymmetric centrosome inheritance leading to neuronal migration delays, and altered neuronal differentiation. Spindle pole localization of WDR62 and mitotic progression are defective in patient-derived fibroblasts, which, similar to mouse neocortical progenitors, transiently arrest at prometaphase...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28270075/comparative-effects-of-polo-like-kinase-1-inhibitors-as-monotherapy-and-in-combination-with-current-treatments-for-medulloblastoma
#13
Julia Alejandra Pezuk, Maria Sol Brassesco, Priscila Maria Manzini Ramos, Carlos Alberto Scrideli, Luiz Gonzaga Tone
BACKGROUND: Medulloblastoma (MB) is one of most frequent malignant tumors that affects children. Despite relative good survival rates, long time sequels are still significant and represent a challenge for treatment of MB patients. Therefore, in an attempt to reduce treatment aftereffects new therapeutic targets are constantly being explored. Polo like kinase 1 (PLK1) is a master cell cycle regulator that has been reported increased in proliferative cells, while its depletion has been repeatedly proposed as an oncological therapeutic strategy...
February 13, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28263958/genomic-instability-during-reprogramming-by-nuclear-transfer-is-dna-replication-dependent
#14
Gloryn Chia, Judith Agudo, Nathan Treff, Mark V Sauer, David Billing, Brian D Brown, Richard Baer, Dieter Egli
Somatic cells can be reprogrammed to a pluripotent state by nuclear transfer into oocytes, yet developmental arrest often occurs. While incomplete transcriptional reprogramming is known to cause developmental failure, reprogramming also involves concurrent changes in cell cycle progression and nuclear structure. Here we study cellular reprogramming events in human and mouse nuclear transfer embryos prior to embryonic genome activation. We show that genetic instability marked by frequent chromosome segregation errors and DNA damage arise prior to, and independent of, transcriptional activity...
March 6, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28262977/metastatic-breast-cancer-cells-enter-into-dormant-state-and-express-cancer-stem-cells-phenotype-under-chronic-hypoxia
#15
Alessandra Carcereri de Prati, Elena Butturini, Antonella Rigo, Elisa Oppici, Michele Rossin, Diana Boriero, Sofia Mariotto
Tumor dormancy is a poorly understood stage in cancer progression characterized by mitotic cycle arrest in G0/G1 phase and low metabolism. The cells survive in a quiescent state and wait for appropriate environmental conditions to begin proliferation again giving rise to metastasis. Despite their key role in cancer development and metastasis, the knowledge about their biology and origin is still very limited due to the poorness of established in vitro models that faithfully recapitulated tumor dormancy. Using at least three cycles of 1%O2 hypoxia and reoxygenation, we establish and characterize the hypoxia-resistant human breast cancer cell line chMDA-MB-231 that can stably survive under 1% O2 condition by entering into dormant state characterized by arrest in G0/G1 phase and low metabolism...
March 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28258163/g-1-inhibits-breast-cancer-cell-growth-via-targeting-colchicine-binding-site-of-tubulin-to-interfere-with-microtubule-assembly
#16
Xiangmin Lv, Chunbo He, Cong Huang, Guohua Hua, Zhengfeng Wang, Steven W Remmenga, Kerry J Rodabaugh, Adam R Karpf, Jixin Dong, John S Davis, Cheng Wang
G-protein coupled estrogen receptor 1 (GPER1) has been reported to play a significant role in mediating the rapid estrogen actions in a wide range of normal and cancer cells. G-1 was initially developed as a selective agonist for GPER. However, the molecular mechanisms underlying the actions of G-1 are unknown and recent studies report inconsistent effects of G-1 on the growth of breast cancer cells. By employing high-resolution laser scanning confocal microscopy and time-lapse imaging technology, as well as biochemical analyses, in the present study, we provide convincing in vitro and in vivo evidence that G-1 is able to suppress the growth of breast cancer cells independent of the expression status of GPERs and classic estrogen receptors...
March 3, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28253265/structurally-simplified-biphenyl-combretastatin-a4-derivatives-retain-in-vitro-anti-cancer-activity-dependent-on-mitotic-arrest
#17
Daniel Tarade, Dennis Ma, Christopher Pignanelli, Fadi Mansour, Daniel Simard, Sean van den Berg, James Gauld, James McNulty, Siyaram Pandey
The cis-stilbene, combretastatin A4 (CA4), is a potent microtubule targeting and vascular damaging agent. Despite promising results at the pre-clinical level and extensive clinical evaluation, CA4 has yet to be approved for therapeutic use. One impediment to the development of CA4 is an inherent conformational instability about the ethylene linker, which joins two aromatic rings. We have previously published preliminary data regarding structurally simplified biphenyl derivatives of CA4, lacking an ethylene linker, which retain anti-proliferative and pro-apoptotic activity, albeit at higher doses...
2017: PloS One
https://www.readbyqxmd.com/read/28249757/suppression-of-spindly-delays-mitotic-exit-and-exacerbates-cell-death-response-of-cancer-cells-treated-with-low-doses-of-paclitaxel
#18
Patrícia M A Silva, Nilza Ribeiro, Raquel T Lima, Cláudia Andrade, Vânia Diogo, Joana Teixeira, Cláudia Florindo, Álvaro Tavares, M Helena Vasconcelos, Hassan Bousbaa
Microtubule-targeting agents (MTAs) are used extensively for the treatment of diverse types of cancer. They block cancer cells in mitosis through the activation of the spindle assembly checkpoint (SAC), the surveillance mechanism that ensures accurate chromosome segregation at the onset of anaphase. However, the cytotoxic activity of MTAs is limited by premature mitotic exit (mitotic slippage) due to SAC silencing. Here we have explored the dual role of the protein Spindly in chromosome attachments and SAC silencing to analyze the consequences of its depletion on the viability of tumor cells treated with clinically relevant doses of paclitaxel...
February 27, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28235409/acetazolamide-potentiates-the-anti-tumor-potential-of-hdaci-ms-275-in-neuroblastoma
#19
Reza Bayat Mokhtari, Narges Baluch, Micky Ka Hon Tsui, Sushil Kumar, Tina S Homayouni, Karen Aitken, Bikul Das, Sylvain Baruchel, Herman Yeger
BACKGROUND: Neuroblastoma (NB), a tumor of the primitive neural crest, despite aggressive treatment portends a poor long-term survival for patients with advanced high stage NB. New treatment strategies are required. METHODS: We investigated coordinated targeting of essential homeostatic regulatory factors involved in cancer progression, histone deacetylases (HDACs) and carbonic anhydrases (CAs). RESULTS: We evaluated the antitumor potential of the HDAC inhibitor (HDACi), pyridylmethyl-N-{4-[(2-aminophenyl)-carbamoyl]-benzyl}-carbamate (MS-275) in combination with a pan CA inhibitor, acetazolamide (AZ) on NB SH-SY5Y, SK-N-SH and SK-N-BE(2) cells...
February 24, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28228549/the-budding-yeast-polo-like-kinase-localizes-to-distinct-populations-at-centrosomes-during-mitosis
#20
Vladimir V Botchkarev, Mikael V Garabedian, Brenda Lemos, Eric Paulissen, James E Haber
The budding yeast Polo-like kinase Cdc5 is a key regulator of many mitotic events. Cdc5 coordinates its functions spatially and temporally by changing its localization during the cell cycle: Cdc5 is imported into the nucleus in G2 phase and is released to the cytoplasm in anaphase, where it accumulates at the bud neck. Cdc5 also localizes to the spindle pole bodies (SPBs) from S phase until the end of mitosis. Whether Cdc5 changes its SPB population during the cell cycle is not known. We find that Cdc5 localizes to distinct SPB subpopulations depending on the mitotic stage...
February 22, 2017: Molecular Biology of the Cell
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