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https://www.readbyqxmd.com/read/29628886/u1-snrnp-alteration-and-neuronal-cell-cycle-reentry-in-alzheimer-disease
#1
REVIEW
Bing Bai
The aberrancy of U1 small nuclear ribonucleoprotein (snRNP) complex and RNA splicing has been demonstrated in Alzheimer's disease (AD). Importantly, the U1 proteopathy is AD-specific, widespread and early-occurring, thus providing a very unique clue to the AD pathogenesis. The prominent feature of U1 histopathology is its nuclear depletion and redistribution in the neuronal cytoplasm. According to the preliminary data, the initial U1 cytoplasmic distribution pattern is similar to the subcellular translocation of the spliceosome in cells undergoing mitosis...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29618387/deregulation-of-the-spindle-assembly-checkpoint-is-associated-with-paclitaxel-resistance-in-ovarian-cancer
#2
Taryne Chong, Amila Sarac, Cindy Q Yao, Linda Liao, Nicola Lyttle, Paul C Boutros, John M S Bartlett, Melanie Spears
BACKGROUND: Ovarian cancer is the leading gynecologic cancer diagnosed in North America and because related symptoms are not disease specific, this often leads to late detection, an advanced disease state, and the need for chemotherapy. Ovarian cancer is frequently sensitive to chemotherapy at diagnosis but rapid development of drug resistance leads to disease progression and ultimately death in the majority of patients. RESULTS: We have generated paclitaxel resistant ovarian cell lines from their corresponding native cell lines to determine driver mechanisms of drug resistance using gene expression arrays...
April 4, 2018: Journal of Ovarian Research
https://www.readbyqxmd.com/read/29607498/1-l-mt-an-ido-inhibitor-prevented-colitis-associated-cancer-by-inducing-cdc20-inhibition-mediated-mitotic-death-of-colon-cancer-cells
#3
Xiuting Liu, Wei Zhou, Xin Zhang, Yang Ding, Qianming Du, Rong Hu
Indoleamine 2,3-dioxygenase 1 (IDO1), known as IDO, catabolizes tryptophan through kynurenine pathway, whose activity is correlated with impaired clinical outcome of colorectal cancer. Here we showed that 1-L-MT, a canonical IDO inhibitor, suppressed proliferation of human colorectal cancer cells through inducing mitotic death. Our results showed that inhibition of IDO decreased the transcription of CDC20, which resulted in G2/M cycle arrest of HCT-116 and HT-29. Furthermore, 1-L-MT induced mitochondria injuries and caused apoptotic cancer cells...
April 1, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29605721/combined-inhibition-of-atr-and-wee1-as-a-novel-therapeutic-strategy-in-triple-negative-breast-cancer
#4
Juan Jin, Hehui Fang, Fang Yang, Wenfei Ji, Nan Guan, Zijia Sun, Yaqin Shi, Guohua Zhou, Xiaoxiang Guan
Triple negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that poses a clinical challenge. Thus, new therapy strategies are urgently needed. The selective WEE1 inhibitor, AZD1775, has shown strong anti-proliferative effects on a variety of tumors. Here, we first demonstrate that inhibition of ATR by selective inhibitor AZD6738 can enhance AZD1775-caused growth inhibition in TNBC. Our results show that the enhanced cell death is attributed to repressed DNA damage repair and excessive replication stress, thereby causing increased DNA damage reflected by accumulation of the DNA double-strand-break marker γH2AX...
March 28, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29604911/extrinsic-and-intrinsic-apoptotic-responses-induced-by-shiitake-culinary-medicinal-mushroom-lentinus-edodes-agaricomycetes-aqueous-extract-against-a-larynx-carcinoma-cell-line
#5
Tiane C Finimundy, Gustavo Scola, Fernando J Scariot, Aldo J P Dillon, Sidnei Moura, Sérgio Echeverrigaray, João Pegas Henriques, Mariana Roesch-Ely
Cumulative evidence from research studies has shown that the shiitake culinary-medicinal mushroom, Lentinus edodes, is an excellent source of natural antitumor agents and is capable of inhibiting cancer cell growth. However, the cell signaling pathway that leads tumor cells to apoptosis is not well understood because many chemical compounds may be acting. This study investigated the chemopreventive effects of an L. edodes aqueous extract on human HEp-2 epithelial larynx carcinoma cells and normal human MRC-5 lung fibroblasts by identifying proliferative and apoptotic pathways...
2018: International Journal of Medicinal Mushrooms
https://www.readbyqxmd.com/read/29602037/synthesis-and-anti-mitotic-activity-of-2-4-or-2-6-disubstituted-and-2-4-6-trisubstituted-2h-pyrazolo-4-3-c-pyridines
#6
Vaida Milišiūnaitė, Eglė Arbačiauskienė, Eva Řezníčková, Radek Jorda, Veronika Malínková, Asta Žukauskaitė, Wolfgang Holzer, Algirdas Šačkus, Vladimír Kryštof
An efficient synthetic route for the synthesis of 2H-pyrazolo[4,3-c]pyridines, primarily varying by the substituents at the 2-, 4- and 6-positions, is described here. A Sonogashira-type cross-coupling reaction was employed to yield 3-alkynyl-1H-pyrazole-4-carbaldehydes, ethanones and propanones from the corresponding 1H-pyrazol-3-yl trifluoromethanesulfonates. Subsequent treatment of the coupling products with dry ammonia afforded a versatile library of 2H-pyrazolo[4,3-c]pyridines, which were then evaluated for their cytotoxicity against K562 and MCF-7 cancer cell lines...
March 16, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29599321/induction-of-mitotic-catastrophe-in-human-cervical-cancer-cells-after-administration-of-aloe-emodin
#7
Wojciech Trybus, Teodora Król, Ewa Trybus, Anna Stachurska, Anna Kopacz-Bednarska, Grzegorz Król
BACKGROUND: Aloe-emodin is an anthraquinone with potential pharmacological properties, including numerous antitumor properties. The purpose of the study was to determine whether aloe-emodin induces mitotic death in cervical cancer cells. MATERIALS AND METHODS: Analysis of morphological changes as surrogate mitotic death indicators in HeLa cells was carried out using optical, fluorescence and electron microscopy. Viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide reduction assay...
April 2018: Anticancer Research
https://www.readbyqxmd.com/read/29593485/-till-death-do-us-part-a-potential-irreversible-link-between-aberrant-cell-cycle-control-and-neurodegeneration-in-the-adult-olfactory-bulb
#8
REVIEW
Saad Omais, Carine Jaafar, Noël Ghanem
Adult neurogenesis (AN) is an ongoing developmental process that generates newborn neurons in the olfactory bulb (OB) and the hippocampus (Hi) throughout life and significantly contributes to brain plasticity. Adult neural stem and progenitor cells (aNSPCs) are relatively limited in number and fate and are spatially restricted to the subventricular zone (SVZ) and the subgranular zone (SGZ). During AN, the distinct roles played by cell cycle proteins extend beyond cell cycle control and constitute key regulatory mechanisms involved in neuronal maturation and survival...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29592883/gallium-maltolate-disrupts-tumor-iron-metabolism-and-retards-the-growth-of-glioblastoma-by-inhibiting-mitochondrial-function-and-ribonucleotide-reductase
#9
Christopher R Chitambar, Mona M Al-Gizawiy, Hisham S Alhajala, Kimberly R Pechman, Janine P Wereley, Robert Wujek, Paul A Clark, John S Kuo, William E Antholine, Kathleen M Schmainda
Gallium, a metal with antineoplastic activity, binds transferrin (Tf) and enters tumor cells via Tf receptor1 (TfR1); it disrupts iron homeostasis leading to cell death. We hypothesized that TfR1 on brain microvascular endothelial cells (BMECs) would facilitate Tf-Ga transport into the brain enabling it to target TfR-bearing glioblastoma. We show that U-87 MG and D54 glioblastoma cell lines and multiple glioblastoma stem cell (GSCs) lines express TfRs and that their growth is inhibited by gallium maltolate (GaM) in vitro...
March 28, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29581894/genetic-and-pharmacological-inhibition-of-cdk1-provides-neuroprotection-towards-ischemic-neuronal-death
#10
Quentin Marlier, Florian Jibassia, Sébastien Verteneuil, Jérôme Linden, Philipp Kaldis, Laurent Meijer, Laurent Nguyen, Renaud Vandenbosch, Brigitte Malgrange
Cell cycle proteins are mainly expressed by dividing cells. However, it is well established that these molecules play additional non-canonical activities in several cell death contexts. Increasing evidence shows expression of cell cycle regulating proteins in post-mitotic cells, including mature neurons, following neuronal insult. Several cyclin-dependent kinases (Cdks) have already been shown to mediate ischemic neuronal death but Cdk1, a major cell cycle G2/M regulator, has not been investigated in this context...
2018: Cell Death Discovery
https://www.readbyqxmd.com/read/29568361/colorectal-cancer-cells-require-glycogen-synthase-kinase-3%C3%AE-for-sustaining-mitosis-via-translocated-promoter-region-tpr-dynein-interaction
#11
Firli R P Dewi, Takahiro Domoto, Masaharu Hazawa, Akiko Kobayashi, Takayuki Douwaki, Toshinari Minamoto, Richard W Wong
Glycogen synthase kinase (GSK) 3β, which mediates fundamental cellular signaling pathways, has emerged as a potential therapeutic target for many types of cancer including colorectal cancer (CRC). During mitosis, GSK3β localizes in mitotic spindles and centrosomes, however its function is largely unknown. We previously demonstrated that translocated promoter region (TPR, a nuclear pore component) and dynein (a molecular motor) cooperatively contribute to mitotic spindle formation. Such knowledge encouraged us to investigate putative functional interactions among GSK3β, TPR, and dynein in the mitotic machinery of CRC cells...
March 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29568313/the-in-vitro-effects-of-a-novel-estradiol-analog-on-cell-proliferation-and-morphology-in-human-epithelial-cervical-carcinoma
#12
Laura Susan Boyd, Devrim Gozuacik, Anna Margaretha Joubert
Background: The majority of novel chemotherapeutics target the cell cycle, aiming to effect arrest and cause apoptosis. One such agent, 2-methoxyestradiol (2ME), has been shown to possess anticancer properties against numerous cancer types, both in vitro and in vivo. Despite its promise, 2ME has exhibited limitations, including low oral bioavailability and rapid hepatic enzymatic inactivation in vivo. A novel sulphamoylated estrogen analog, 2-ethyl-3- O -sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16), was in silico-designed in our laboratory to overcome these issues...
2018: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/29562589/an-interplay-between-senescence-apoptosis-and-autophagy-in-glioblastoma-multiforme-role-in-pathogenesis-and-therapeutic-perspective
#13
REVIEW
Elzbieta Pawlowska, Joanna Szczepanska, Magdalena Szatkowska, Janusz Blasiak
Autophagy, cellular senescence, programmed cell death and necrosis are key responses of a cell facing a stress. These effects are partly interconnected, but regulation of their mutual interactions is not completely clear. That regulation seems to be especially important in cancer cells, which have their own program of development and demand more nutrition and energy than normal cells. Glioblastoma multiforme (GBM) belongs to the most aggressive and most difficult to cure cancers, so studies on its pathogenesis and new therapeutic strategies are justified...
March 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29556720/polymyxin-b-causes-dna-damage-in-hk-2-cells-and-mice
#14
B Yun, T Zhang, M A K Azad, J Wang, C J Nowell, P Kalitsis, T Velkov, D F Hudson, J Li
Increasing incidence of multidrug-resistant bacteria presents an imminent risk to global health. Polymyxins are 'last-resort' antibiotics against Gram-negative 'superbugs'; however, nephrotoxicity remains a key impediment in their clinical use. Molecular mechanisms underlying this nephrotoxicity remain poorly defined. Here, we examined the pathways which led to polymyxin B induced cell death in vitro and in vivo. Human proximal tubular cells were treated with polymyxin B (12.5-100 μM) for up to 24 h and showed a significant increase in micronuclei frequency, as well as abnormal mitotic events (over 40% in treated cells, p < 0...
March 20, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29555944/scoulerine-affects-microtubule-structure-inhibits-proliferation-arrests-cell-cycle-and-thus-culminates-in-the-apoptotic-death-of-cancer-cells
#15
Klara Habartova, Radim Havelek, Martina Seifrtova, Karel Kralovec, Lucie Cahlikova, Jakub Chlebek, Eva Cermakova, Nadezda Mazankova, Jana Marikova, Jiri Kunes, Lucie Novakova, Martina Rezacova
Scoulerine is an isoquinoline alkaloid, which indicated promising suppression of cancer cells growth. However, the mode of action (MOA) remained unclear. Cytotoxic and antiproliferative properties were determined in this study. Scoulerine reduces the mitochondrial dehydrogenases activity of the evaluated leukemic cells with IC50 values ranging from 2.7 to 6.5 µM. The xCELLigence system revealed that scoulerine exerted potent antiproliferative activity in lung, ovarian and breast carcinoma cell lines. Jurkat and MOLT-4 leukemic cells treated with scoulerine were decreased in proliferation and viability...
March 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29555478/inhibition-of-tacc3-by-a-small-molecule-inhibitor-in-breast-cancer
#16
Loredana Campo, Eun-Kyoung Breuer
Studies have shown that transforming acidic coiled-coil protein 3 (TACC3), a key component of centrosome-microtubule dynamic networks, is significantly associated with various types of human cancer. We have recently reported that high levels of TACC3 are found in breast cancer, lead to the accumulation of spontaneous DNA damage due to defective DNA damage response signaling, and confer cellular sensitivity to radiation and poly(ADP-ribose) polymerase (PARP) inhibitors. Although our study suggests a potential role of TACC3 as a biomarker in breast cancer detection and prediction of therapy outcome, its role as a therapeutic target in breast cancer is not well studied...
March 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29515122/pan-class-i-pi3-kinase-inhibitor-bkm120-induces-mek1-2-dependent-mitotic-catastrophe-in-non-hodgkin-lymphoma-leading-to-apoptosis-or-polyploidy-determined-by-bax-bak-and-p53
#17
Anja Müller, Bernd Gillissen, Antje Richter, Anja Richter, Cindrilla Chumduri, Peter T Daniel, Christian W Scholz
Constitutive signaling of PI3K/Akt/mTOR plays a prominent role in malignant transformation and progression of B-cell non-Hodgkin lymphomas (B-NHL) underscoring the need for PI3K targeted therapies. The pan-class I PI3-kinase inhibitor BKM120 has shown preclinical activity in distinct malignancies and is currently tested in clinical trials. Intratumor heterogeneity is an intrinsic property of cancers that contributes to drug resistance and tumor recurrence. Here, we demonstrate that inhibition of PI3-kinases by BKM120 attenuates growth and survival of B-NHL cell lines by inducing mitotic arrest with subsequent induction of intrinsic apoptosis...
March 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29497138/anti-mitotic-chemotherapeutics-promote-apoptosis-through-tl1a-activated-death-receptor-3-in-cancer-cells
#18
Chen Qi, Xin Wang, Zhirong Shen, She Chen, Hong Yu, Noelle Williams, Gelin Wang
The commonly used antimitotic chemotherapeutic agents such as taxol and vinblastine arrest cell cycle progression by disrupting mitotic spindles, and cause cancer cells to undergo apoptosis through 'mitotic catastrophe'. The molecular mechanisms by which these drugs induce apoptosis and their relevance to clinical efficacy are not known. Facilitated by a new spindle poison diazonamide, we found that apoptosis induced by these agents requires death receptor 3 (DR3). Mitotic arrest by these agents induces lysosome-dependent secretion of the DR3 ligand, TL1A...
March 1, 2018: Cell Research
https://www.readbyqxmd.com/read/29487893/ubash3b-mediated-silencing-of-the-mitotic-checkpoint-therapeutic-perspectives-in-cancer
#19
Ksenia Krupina, Charlotte Kleiss, Sushil Awal, Irene Rodriguez-Hernandez, Victoria Sanz-Moreno, Izabela Sumara
Defects in mitosis can lead to aneuploidy, which is a common feature of human cancers. Spindle Assembly Checkpoint (SAC) controls fidelity of chromosome segregation in mitosis to prevent aneuploidy. The ubiquitin receptor protein Ubiquitin Associated and SH3 Domain Containing B (UBASH3B) was recently found to control SAC silencing and faithful chromosome segregation by relocalizing Aurora B kinase to the mitotic microtubules. Accordingly, loss and gain of function of UBASH3B have strong effects on mitotic progression...
2018: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/29477556/stochastic-cellular-automata-model-of-neurosphere-growth-roles-of-proliferative-potential-contact-inhibition-cell-death-and-phagocytosis
#20
Rifat Sipahi, Günther K H Zupanc
Neural stem and progenitor cells isolated from the central nervous system form, under specific culture conditions, clonal cell clusters known as neurospheres. The neurosphere assay has proven to be a powerful in vitro system to study the behavior of such cells and the development of their progeny. However, the theory of neurosphere growth has remained poorly understood. To overcome this limitation, we have, in the present paper, developed a cellular automata model, with which we examined the effects of proliferative potential, contact inhibition, cell death, and clearance of dead cells on growth rate, final size, and composition of neurospheres...
February 22, 2018: Journal of Theoretical Biology
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