scholarly journals Arl2 and Arl3 Regulate Different Microtubule-dependent Processes

2006 ◽  
Vol 17 (5) ◽  
pp. 2476-2487 ◽  
Author(s):  
Chengjing Zhou ◽  
Leslie Cunningham ◽  
Adam I. Marcus ◽  
Yawei Li ◽  
Richard A. Kahn
Keyword(s):  
Common Ancestor ◽  
Tubulin Polymerization ◽  
Mitotic Spindles ◽  
Eukaryotic Evolution ◽  
Cycle Arrest ◽  
Initial Characterization ◽  
M Phase ◽  
Functional Features ◽  
Dependent Processes

Arl2 and Arl3 are closely related members of the Arf family of regulatory GTPases that arose from a common ancestor early in eukaryotic evolution yet retain extensive structural, biochemical, and functional features. The presence of Arl3 in centrosomes, mitotic spindles, midzones, midbodies, and cilia are all supportive of roles in microtubule-dependent processes. Knockdown of Arl3 by siRNA resulted in changes in cell morphology, increased acetylation of α-tubulin, failure of cytokinesis, and increased number of binucleated cells. We conclude that Arl3 binds microtubules in a regulated manner to alter specific aspects of cytokinesis. In contrast, an excess of Arl2 activity, achieved by expression of the [Q70L]Arl2 mutant, caused the loss of microtubules and cell cycle arrest in M phase. Initial characterization of the underlying defects suggests a defect in the ability to polymerize tubulin in the presence of excess Arl2 activity. We also show that Arl2 is present in centrosomes and propose that its action in regulating tubulin polymerization is mediated at centrosomes. Somewhat paradoxically, no phenotypes were observed Arl2 expression was knocked down or Arl3 activity was increased in HeLa cells. We conclude that Arl2 and Arl3 have related but distinct roles at centrosomes and in regulating microtubule-dependent processes.

scholarly journals Cell Cycle Synchrony in Giardia intestinalis Cultures Achieved by Using Nocodazole and Aphidicolin

2008 ◽  
Vol 7 (4) ◽  
pp. 569-574 ◽  
Author(s):  
Marianne K. Poxleitner ◽  
Scott C. Dawson ◽  
W. Zacheus Cande
Keyword(s):  
Cell Cycle ◽  
Model Organism ◽  
Protozoan Parasite ◽  
Giardia Intestinalis ◽  
Mitotic Spindles ◽  
Intestinal Protozoan ◽  
Cycle Arrest ◽  
Cycle Dependent ◽  
Dependent Processes

ABSTRACT Giardia intestinalis is a ubiquitous intestinal protozoan parasite and has been proposed to represent the earliest diverging lineage of extant eukaryotes. Despite the importance of Giardia as a model organism, research on Giardia has been hampered by an inability to achieve cell cycle synchrony for in vitro cultures. This report details successful methods for attaining cell cycle synchrony in Giardia cultures. The research presented here demonstrates reversible cell cycle arrest in G1/S and G2/M with aphidicolin and nocodazole, respectively. Following synchronization, cells were able to recover completely from drug treatment and remained viable and maintained synchronous growth for 6 h. These techniques were used to synchronize Giardia cultures to increase the percentages of mitotic spindles in the cultures. This method of synchronization will enhance our ability to study cell cycle-dependent processes in G. intestinalis.

scholarly journals Cucurbitacins: elucidation of their interactions with the cytoskeleton

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3357 ◽  
Author(s):  
Xiaojuan Wang ◽  
Mine Tanaka ◽  
Herbenya Silva Peixoto ◽  
Michael Wink
Keyword(s):  
Actin Filaments ◽  
Living Cells ◽  
Cytoskeletal Proteins ◽  
Microtubule Assembly ◽  
Tubulin Polymerization ◽  
Mitotic Spindles ◽  
Cucurbitacin B ◽  
M Phase ◽  
Cucurbitacin E

Cucurbitacins, a class of toxic tetracyclic triterpenoids in Cucurbitaceae, modulate many molecular targets. Here we investigated the interactions of cucurbitacin B, E and I with cytoskeletal proteins such as microtubule and actin filaments. The effects of cucurbitacin B, E and I on microtubules and actin filaments were studied in living cells (Hela and U2OS) and in vitro using GFP markers, immunofluorescence staining and in vitro tubulin polymerization assay. Cucurbitacin B, E and I apparently affected microtubule structures in living cells and cucurbitacin E inhibited tubulin polymerization in vitro with IC50 value of 566.91 ± 113.5 µM. Cucurbitacin E did not affect the nucleation but inhibited the growth phase and steady state during microtubule assembly in vitro. In addition, cucurbitacin B, E and I all altered mitotic spindles and induced the cell cycle arrest at G2/M phase. Moreover, they all showed potent effects on actin cytoskeleton by affecting actin filaments through the depolymerization and aggregation. The interactions of cucubitacin B, E and I with microtubules and actin filaments present new insights into their modes of action.

Synthesis of novel aryl dithian valeryl podophyllotoxin ester derivatives as potential antitubulin agents

RSC Advances ◽  
2015 ◽  
Vol 5 (59) ◽  
pp. 47511-47521 ◽  
Author(s):  
Hong-Yan Lin ◽  
Zi-Kang Li ◽  
Hong-Wei Han ◽  
Han-Yue Qiu ◽  
Hong-Wei Gu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
A549 Cell ◽  
Tubulin Polymerization ◽  
Cycle Arrest ◽  
M Phase

L4 can cause A549 cell cycle arrest in the G2/M phase potently by disrupting tubulin polymerization.

scholarly journals Potent Quinoline-Containing Combretastatin A-4 Analogues: Design, Synthesis, Antiproliferative, and Anti-Tubulin Activity

2020 ◽  
Vol 13 (11) ◽  
pp. 393
Author(s):  
Tarek S. Ibrahim ◽  
Mohamed M. Hawwas ◽  
Azizah M. Malebari ◽  
Ehab S. Taher ◽  
Abdelsattar M. Omar ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Tubulin Polymerization ◽  
Design Synthesis ◽  
Cycle Arrest ◽  
M Phase ◽  
Ic50 Values ◽  
Low Cytotoxicity ◽  
Induced Apoptosis ◽  
Derivatives Of ◽  
Mcf 7

A novel series of quinoline derivatives of combretastatin A-4 incorporating rigid hydrazone and a cyclic oxadiazole linkers were synthesized and have demonstrated potent tubulin polymerization inhibitory properties. Many of these novel derivatives have shown significant antiproliferative activities in the submicromolar range. The most potent compound, 19h, demonstrated superior IC50 values ranging from 0.02 to 0.04 µM against four cancer cell lines while maintaining low cytotoxicity in MCF-10A non-cancer cells, thereby suggesting 19h’s selectivity towards proliferating cancer cells. In addition to tubulin polymerization inhibition, 19h caused cell cycle arrest in MCF-7 cells at the G2/M phase and induced apoptosis. Collectively, these findings indicate that 19h holds potential for further investigation as a potent chemotherapeutic agent targeting tubulin.

CHARACTERIZATION OF RELIGIOUS STYLE AS A FUNCTIONAL STYLE IN LINGUISTICS

2020 ◽  
Vol 1 (3) ◽  
pp. 236-242
Author(s):  
Barnokhon Kushakova ◽  
Keyword(s):  
Social Life ◽  
Religious Language ◽  
Religious Texts ◽  
World Outlook ◽  
The People ◽  
The Social ◽  
Functional Features ◽  
The Creation

This article discusses the conditions, reasons and factors of characterization of religious style as a functional style in the field of linguistics. In addition, religious style and its main peculiarities, its importance in the social life, and the functional features of religious style are highlighted in the article. As a result of our investigation, the following results were obtained: a) the increase in the need for the creation and significance of religious language, particularly religious texts has been scientifically proved; b) the possibility of religious texts to represent the thoughts of the people, culture and world outlook has been verified; c) the specificity of religious language, religious texts has been revealed; d) the development of religious style as a functional style has been grounded.

Alkylphospholipids are Signal Transduction Modulators with Potential for Anticancer Therapy

2019 ◽  
Vol 19 (1) ◽  
pp. 66-91 ◽  
Author(s):  
Ferda Kaleağasıoğlu ◽  
Maya M. Zaharieva ◽  
Spiro M. Konstantinov ◽  
Martin R. Berger
Keyword(s):  
Clinical Success ◽  
Phase Cell ◽  
Akt Phosphorylation ◽  
Cycle Arrest ◽  
M Phase ◽  
Mtor Phosphorylation ◽  
Antiviral Activities ◽  
Bone Marrow Sparing ◽  
Membrane Components ◽  
The Way

Background:Alkylphospholipids (APLs) are synthetically derived from cell membrane components, which they target and thus modify cellular signalling and cause diverse effects. This study reviews the mechanism of action of anticancer, antiprotozoal, antibacterial and antiviral activities of ALPs, as well as their clinical use.Methods:A literature search was used as the basis of this review.Results:ALPs target lipid rafts and alter phospholipase D and C signalling cascades, which in turn will modulate the PI3K/Akt/mTOR and RAS/RAF/MEK/ERK pathways. By feedback coupling, the SAPK/JNK signalling chain is also affected. These changes lead to a G2/M phase cell cycle arrest and subsequently induce programmed cell death. The available knowledge on inhibition of AKT phosphorylation, mTOR phosphorylation and Raf down-regulation renders ALPs as attractive candidates for modern medical treatment, which is based on individualized diagnosis and therapy. Corresponding to their unusual profile of activities, their side effects result from cholinomimetic activity mainly and focus on the gastrointestinal tract. These aspects together with their bone marrow sparing features render APCs well suited for modern combination therapy. Although the clinical success has been limited in cancer diseases so far, the use of miltefosine against leishmaniosis is leading the way to better understanding their optimized use.Conclusion:Recent synthetic programs generate congeners with the increased therapeutic ratio, liposomal formulations, as well as diapeutic (or theranostic) derivatives with optimized properties. It is anticipated that these innovative modifications will pave the way for the further successful development of ALPs.

Hybridized Quinoline Derivatives as Anticancer Agents: Design, Synthesis, Biological Evaluation and Molecular Docking

2019 ◽  
Vol 19 (4) ◽  
pp. 439-452 ◽  
Author(s):  
Mohamed R. Selim ◽  
Medhat A. Zahran ◽  
Amany Belal ◽  
Moustafa S. Abusaif ◽  
Said A. Shedid ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Anticancer Agents ◽  
Caspase 3 ◽  
Biological Evaluation ◽  
Tubulin Polymerization ◽  
Design Synthesis ◽  
Chemical Structures ◽  
M Phase ◽  
Induced Apoptosis ◽  
Derivatives Of

Objective: Conjugating quinolones with different bioactive pharmacophores to obtain potent anticancer active agents. Methods: Fused pyrazolopyrimidoquinolines 3a-d, Schiff bases 5, 6a-e, two hybridized systems: pyrazolochromenquinoline 7 and pyrazolothiazolidinquinoline 8, different substituted thiazoloquinolines 13-15 and thiazolo[3,2-a]pyridine derivatives 16a-c were synthesized. Their chemical structures were characterized through spectral and elemental analysis, cytotoxic activity on five cancer cell lines, caspase-3 activation, tubulin polymerization inhibition and cell cycle analysis were evaluated. Results: Four compounds 3b, 3d, 8 and 13 showed potent activity than doxorubicin on HCT116 and three compounds 3b, 3d and 8 on HEPG2. These promising derivatives showed increase in the level of caspase-3. The trifloromethylphenyl derivatives of pyrazolopyrimidoquinolines 3b and 3d showed considerable tubulin polymerization inhibitory activity. Both compounds arrested cell cycle at G2/M phase and induced apoptosis. Conclusion: Compounds 3b and 3d can be considered as promising anticancer active agents with 70% of colchicine activity on tubulin polymerization inhibition and represent hopeful leads that deserve further investigation and optimization.

scholarly journals The Antiproliferative Activity of Oxypeucedanin via Induction of G2/M Phase Cell Cycle Arrest and p53-Dependent MDM2/p21 Expression in Human Hepatoma Cells

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 501
Author(s):  
So Hyun Park ◽  
Ji-Young Hong ◽  
Hyen Joo Park ◽  
Sang Kook Lee
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Antiproliferative Activity ◽  
Hepatoma Cells ◽  
Phase Cell ◽  
Human Hepatoma Cells ◽  
Cycle Arrest ◽  
Growth Inhibitory Activity ◽  
M Phase

Oxypeucedanin (OPD), a furocoumarin compound from Angelica dahurica (Umbelliferae), exhibits potential antiproliferative activities in human cancer cells. However, the underlying molecular mechanisms of OPD as an anticancer agent in human hepatocellular cancer cells have not been fully elucidated. Therefore, the present study investigated the antiproliferative effect of OPD in SK-Hep-1 human hepatoma cells. OPD effectively inhibited the growth of SK-Hep-1 cells. Flow cytometric analysis revealed that OPD was able to induce G2/M phase cell cycle arrest in cells. The G2/M phase cell cycle arrest by OPD was associated with the downregulation of the checkpoint proteins cyclin B1, cyclin E, cdc2, and cdc25c, and the up-regulation of p-chk1 (Ser345) expression. The growth-inhibitory activity of OPD against hepatoma cells was found to be p53-dependent. The p53-expressing cells (SK-Hep-1 and HepG2) were sensitive, but p53-null cells (Hep3B) were insensitive to the antiproliferative activity of OPD. OPD also activated the expression of p53, and thus leading to the induction of MDM2 and p21, which indicates that the antiproliferative activity of OPD is in part correlated with the modulation of p53 in cancer cells. In addition, the combination of OPD with gemcitabine showed synergistic growth-inhibitory activity in SK-Hep-1 cells. These findings suggest that the anti-proliferative activity of OPD may be highly associated with the induction of G2/M phase cell cycle arrest and upregulation of the p53/MDM2/p21 axis in SK-HEP-1 hepatoma cells.

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