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Mitotic arrest

Elizabeth Thomas, Vidya Gopalakrishnan, Mahesh Hegde, Sujeet Kumar, Subhas S Karki, Sathees C Raghavan, Bibha Choudhary
Resveratrol is one of the most widely studied bioactive plant polyphenols which possesses anticancer properties. Previously we have reported synthesis, characterization and identification of a novel resveratrol analog, SS28. In the present study, we show that SS28 induced cytotoxicity in several cancer cell lines ex vivo with an IC50 value of 3-5 μM. Mechanistic evaluation of effect of SS28 in non-small cell lung cancer cell line (A549) and T-cell leukemic cell line (CEM) showed that it inhibited Tubulin polymerization during cell division to cause cell cycle arrest at G2/M phase of the cell cycle at 12-18 h time period...
October 17, 2016: Scientific Reports
Suthakar Ganapathy, Johan B Fagman, Ling Shen, Tianqi Yu, Xiaodong Zhou, Wei Dai, Alexandros Makriyannis, Changyan Chen
Nf1 mutations or deletions are suggested to underlie the tumor predisposition of NF1 (neurofibromatosis type 1) and few treatments are available for treating NF1 patients with advanced malignant tumors. Aberrant activation of Ras in Nf1-deficient conditions is responsible for the promotion of tumorigenesis in NF1. PKC is proven to be an important factor in supporting the viability of Nf1-defected cells, but the molecular mechanisms are not fully understood. In this study, we demonstrate that the inhibition of protein kinase C (PKC) by 1-O-Hexadecyl-2-O-methyl-rac-glycerol (HMG, a PKC inhibitor) preferentially sensitizes Nf1-defected cells to apoptosis, via triggering a persistent mitotic arrest...
October 12, 2016: Oncotarget
Yunhui Li, Minhui Zhang, Shaojun Li, Rongrong Lv, Pan Chen, Ran Liu, Geyu Liang, Lihong Yin
There is increasing evidence that epoxiconazole exposure can affect reproductive function, but few studies have investigated adverse effects on spermatogenesis. The nematode Caenorhabditis elegans (C. elegans) was used in our study to assess effects of epoxiconazole on spermatogenesis in male nematodes after 48 h of exposure to concentrations of 0.1, 1.0, or 10.0 μg/L. The results demonstrated that epoxiconazole exposure affected spermatogenesis, decreasing the number of total germ cells, mitotic cells, meiotic cells and spermatids, spermatid diameter, and cross-sectional area, and inducing mitotic germ cell proliferation arrest, premature entry into meiosis, and sperm activation inhibition; however, sperm transfer showed no abnormal changes...
October 8, 2016: International Journal of Environmental Research and Public Health
Gianandrea Traversi, Mario Fiore, Zulema Percario, Francesca Degrassi, Renata Cozzi
Natural compounds are extensively studied for their potential use in traditional and non-traditional medicine. Several natural and synthetic Resveratrol analogues have shown interesting biological activities in the field of cancer chemoprevention. In the present study, we have focused on the ability of Resveratrol and two methoxylated derivatives (Trimethoxystilbene and Pterostilbene) to inhibit human cancer cell growth particularly analyzing their ability to interfere with tubulin dynamics at mitosis. We show that Trimethoxystilbene, differently from Resveratrol and Pterostilbene, alters microtubule polymerization dynamics in HeLa cells specifically inducing multipolar spindles and mitotic arrest coupled to a reduction of cell growth and an increase in apoptotic death by mitotic catastrophe...
October 14, 2016: Molecular Carcinogenesis
Rong Chu, Sarah E Alford, Katherine Hart, Anisha Kothari, Samuel G Mackintosh, Matthew R Kovak, Timothy C Chambers
Microtubule targeting agents (MTAs) characteristically promote phosphorylation and degradation of Mcl-1, and this represents a critical pro-apoptotic signal in mitotic death. While several phosphorylation sites and kinases have been implicated in mitotic arrest-induced Mcl-1 phosphorylation, a comprehensive biochemical analysis has been lacking. Contrary to previous reports suggesting that T92 phosphorylation by Cdk1 regulates Mcl-1 degradation, a T92A Mcl-1 mutant expressed in HeLa cells was phosphorylated and degraded with the same kinetics as wild-type Mcl-1 following vinblastine treatment...
October 12, 2016: Oncotarget
Seongyeong Kim, Ahrum Min, Kyung-Hun Lee, Yaewon Yang, Tae-Yong Kim, Jee Min Lim, So Jung Park, Hyun-Jin Nam, Jung Eun Kim, Sang-Hyun Song, Sae-Won Han, Do-Youn Oh, Jee Hyun Kim, Tae-You Kim, David Hangauer, Johnson Yiu-Nam Lau, Kyongok Im, Dong Soon Lee, Yung-Jue Bang, Seock-Ah Im
Purpose: KX-01 is a novel dual inhibitor of Src and tubulin. Unlike previous Src inhibitors that failed to show clinical benefit during treatment of breast cancer, KX-01 can potentially overcome the therapeutic limitations of current Src inhibitors through inhibition of both Src and tubulin. The present study further evaluates the activity and mechanism of KX-01 in vitro and in vivo. Materials and Methods: The anti-tumor effect of KX-01 in triple negative breast cancer (TNBC) cell lines was determined by MTT assay...
October 6, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Katharina Müller, Philipp M Klein, Philipp Heissig, Andreas Roidl, Ernst Wagner
Antitumoral siRNA and miRNA delivery was demonstrated by epidermal growth factor receptor (EGFR) targeted oligoaminoamide polyplexes. For this purpose, the T-shaped lipo-oligomer 454 was used to complex RNA into a core polyplex, which was subsequently functionalized with the targeting peptide ligand GE11 via a polyethylene glycol (PEG) linker. To this end, free cysteines on the surface of 454 polyplex were coupled with a maleimide-PEG-GE11 reagent (Mal-GE11). Resulting particles with sizes of 120-150 nm showed receptor-mediated uptake into EGFR-positive T24 bladder cancer cells, MDA-MB 231 breast cancer cells and Huh7 liver cancer cells...
October 13, 2016: Nanotechnology
Shuai Hou, Na Li, Qian Zhang, Hui Li, Xinyue Wei, Tian Hao, Yue Li, Sikandar Azam, Caigang Liu, Wei Cheng, Bilian Jin, Quentin Liu, Man Li, Haixin Lei
Xeroderma pigmentosum group A (XPA)-binding protein 2 (XAB2) is a multi-functional protein that plays critical role in processes including transcription, transcription-coupled DNA repair, pre-mRNA splicing, homologous recombination and mRNA export. Microarray analysis on gene expression in XAB2 knockdown cells reveals that many genes with significant change in expression function in mitotic cell cycle regulation. Fluorescence-activated cell scanner analysis confirmed XAB2 depletion led to cell arrest in G2/M phase, mostly at prophase or prometaphase...
October 13, 2016: Cell Death & Disease
Victor V Semenov, Boris V Lichitsky, Andrey N Komogortsev, Arkady A Dudinov, Mikhail M Krayushkin, Leonid D Konyushkin, Olga P Atamanenko, Irina B Karmanova, Yuri A Strelenko, Boris Shor, Marina N Semenova, Alex S Kiselyov
A series of 3,7-diaryl-6,7-dihydroisothiazolo [4,5-b]pyridin-5(4H)-ones 8 and 9 was synthesized by multicomponent condensation of 3-aryl-5-isothiazolecarboxylic acid esters 4a-f with aromatic (or thienyl) aldehydes 7 and Meldrum's acid in an acidic medium. The targeted compounds were evaluated for their antimitotic microtubule destabilizing activity using in vivo phenotypic sea urchin embryo model and in vitro human cancer cell-based assays. Selected dihydroisothiazolopyridinones altered sea urchin egg cleavage in 2-10 nM concentrations together with significant cytotoxicity against cancer cells including chemoresistant cell lines (IC50 in submicromolar - low nanomolar concentration range)...
September 24, 2016: European Journal of Medicinal Chemistry
Andreas Ritter, Alexandra Friemel, Nina-Naomi Kreis, Frank Louwen, Juping Yuan
Polo-like kinase 1 (Plk1) has been established as one of the most promising targets for molecular anticancer intervention. In fact, various Plk1 inhibitors have been identified and characterized. While the data derived from the bench are prospective, the clinical outcomes are less encouraging by showing modest efficacy. One of the explanations for this discrepancy could be unintendedly targeting of non-malignant cells by Plk1 inhibitors. In this work, we have addressed the effect of Plk1 inhibition in adipose tissue-derived mesenchymal stem cells (ASCs)...
October 5, 2016: Oncotarget
Chuangyu Wen, Junxiong Chen, Di Zhang, Huihui Wang, Jia Che, Qiyuan Qin, Lu He, Zerong Cai, Mengmeng Lin, Qiong Lou, Lanlan Huang, Daici Chen, Aikichi Iwamoto, Donglin Ren, Lei Wang, Ping Lan, Jianping Wang, Huanliang Liu, Xiangling Yang
5-fluorouracil (5-FU)-based chemotherapy is the main chemotherapeutic approach for colorectal cancer (CRC) treatment. Because chemoresistance occurs frequently and significantly limits CRC therapies, a novel agent is needed. Pseudolaric acid B (PAB), a small molecule derived from the Chinese medicinal herb ''Tujinpi'', exhibits strong cytotoxic effects on a variety of cancers. However, the detailed mechanisms by which PAB inhibits CRC cell growth and its potential role in overcoming 5-FU resistance have not been well studied...
October 3, 2016: Cancer Letters
Vanessa Pierroz, Riccardo Rubbiani, Christian Gentili, Malay Patra, Cristina Mari, Gilles Gasser, Stefano Ferrari
Photodynamic therapy (PDT) is an attractive, complementary medical technique to chemotherapy. Among the different photosensitizers (PSs) employed, Ru(ii) polypyridyl complexes were found to be valid substitutes to porphyrin-based or phthalocyanine-based PSs. Here, we confirm that one such complex, namely [Ru(bipy)2-dppz-7-methoxy][PF6]2 (Ru65), which localizes in the nucleus of various cancer and normal cells, displays cytotoxicity only upon UV-A irradiation. Importantly, we disclose the molecular mechanism of the UV-A mediated cytotoxic action of Ru65...
August 16, 2016: Chemical Science
Junguo Wang, Fang Mei, Xia Gao, Shoulin Wang
Nasopharyngeal carcinoma (NPC) is the most common cancer originating from the nasopharynx, and can be induced by infection with Epstein-Barr virus (EBV). To study the mechanisms of EBV-associated NPC, a microarray of the GSE12452 dataset was analyzed. GSE12452 was downloaded from Gene Expression Omnibus and consisted of 31 NPC samples and 10 normal healthy nasopharyngeal tissue samples. The differentially-expressed genes (DEGs) were screened using the linear models for microarray data package in R. Using Database for Annotation, Visualization and Integrated Discovery software, potential functions of the DEGs were predicted by Gene Ontology and pathway enrichment analyses...
October 2016: Oncology Letters
Nisha A Lakhi, Gerald J Mizejewski
Elevations of serum alpha-fetoprotein (sAFP) have been reported in fetal and infant states of anemia. Fanconi anemia (FA) belongs to a family of genetic instability disorders which lack the capability to repair DNA breaks. The lesion occurs at a checkpoint regulatory step of the G2 to mitotic transition, allowing FA cells to override cell-cycle arrest. FA DNA repair pathways contain complementation groups known as FANC proteins. FANC proteins form multi-protein complexes with BRCA proteins and are involved in homologous DNA repair...
October 3, 2016: Fetal and Pediatric Pathology
Martin Převorovský, Martina Oravcová, Róbert Zach, Anna Jordáková, Jürg Bähler, František Půta, Petr Folk
For every eukaryotic cell to grow and divide, intricately coordinated action of numerous proteins is required to ensure proper cell-cycle progression. The fission yeast Schizosaccharomyces pombe has been instrumental in elucidating the fundamental principles of cell-cycle control. Mutations in S. pombe 'cut' (cell untimely torn) genes cause failed coordination between cell and nuclear division, resulting in catastrophic mitosis. Deletion of cbf11, a fission yeast CSL transcription factor gene, triggers a 'cut' phenotype, but the precise role of Cbf11 in promoting mitotic fidelity is not known...
September 29, 2016: Cell Cycle
Jillian W Millsop, Victoria R Sharon, Tatyana Petukhova, Maxwell A Fung, Maija Kiuru
The histopathologic characteristics of reactions caused by the many novel anticancer agents are under-recognized. We report a case of a 67-year-old female with locally advanced metastatic breast cancer, who initially presented with an extensive reticulated erythematous patch on the trunk caused by intravascular metastases confirmed by a skin biopsy. Due to disease progression, she was started on ixabepilone, a mitotic inhibitor. While receiving ixabepilone, another skin biopsy was obtained and initially interpreted as extramammary Paget's disease...
September 30, 2016: Journal of Cutaneous Pathology
Jinhua Zhou, Albandri Alfraidi, Shu Zhang, Janice Santiago-O'Farrill, Venkata Yerramreddy, Abdulkhaliq Alsaadid, Ahmed Ashour Ahmed, Hailing Yang, Jinsong Liu, Weiqun Mao, Hiroshi Takemori, Yan Wang, Hariprasad Vankayalapati, Zhen Lu, Robert C Bast
PURPOSE: SIK2 is a centrosome kinase required for mitotic spindle formation and a potential target for ovarian cancer therapy. Here we examine the effects of a novel small molecule SIK2 inhibitor, ARN-3236, on sensitivity to paclitaxel in ovarian cancer. EXPERIMENTAL DESIGN: SIK2 expression was determined in ovarian cancer tissue samples and cell lines. ARN-3236 was tested for its efficiency to inhibit growth and enhance paclitaxel sensitivity in cultures and xenografts of ovarian cancer cell lines...
September 27, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Soo Hwa Jang, Ah-Ram Kim, Neung-Hwa Park, Jeong Woo Park, In-Seob Han
Developmentally regulated GTP-binding protein 2 (DRG2) plays an important role in cell growth. Here we explored the linkage between DRG2 and G2/M phase checkpoint function in cell cycle progression. We observed that knockdown of DRG2 in HeLa cells affected growth in a wound-healing assay, and tumorigenicity in nude mice xenografts. Flow cytometry assays and [(3)H] incorporation assays indicated that G2/M phase arrest was responsible for the decreased proliferation of these cells. Knockdown of DRG2 elicited down-regulation of the major mitotic promoting factor, the cyclin B1/Cdk1 complex, but up-regulation of the cell cycle arresting proteins, Wee1, Myt1, and p21...
September 2016: Molecules and Cells
Gaurav Kumar Singh, Sharanbasappa Shrimant Karade, Rajeev Ranjan, Nafees Ahamad, Shakil Ahmed
The mitotic arrest deficiency 2 (Mad2) protein is an essential component of the spindle assembly checkpoint that interacts with Cdc20/Slp1 and inhibit its ability to activate anaphase promoting complex/cyclosome (APC/C). In bladder cancer cell line the C-terminal residue of the mad2 gene has been found to be deleted. In this study we tried to understand the role of the C-terminal region of mad2 on the spindle checkpoint function. To envisage the role of C-terminal region of Mad2, we truncated 25 residues of Mad2 C-terminal region in fission yeast S...
September 23, 2016: Molecular Biology Reports
Yoshie A Fujioka, Asuka Onuma, Wataru Fujii, Koji Sugiura, Kunihiko Naito
Cyclin B (CCNB) accumulation is essential for regulating maturation/M-phase promoting factor activity during vertebrate oocyte maturation. Anaphase-promoting-complex/cyclosome (APC/C) degrades CCNB, allowing the cell cycle to progress; this complex is inhibited by Early mitotic inhibitors 1 and 2 (EMI1 and EMI2). The involvement of both EMI proteins in meiotic maturation has been reported in Xenopus and mouse oocytes, although a recent study described a marked difference in their respective function during meiotic resumption...
September 20, 2016: Molecular Reproduction and Development
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