scholarly journals A Novel M-phase Inhibitor DEA-1496

2017 ◽  
Vol 06 (01) ◽  
Author(s):  
Masahiko Morioka
Keyword(s):  
M Phase

Meiotic CENP-C is a shepherd: bridging the space between the centromere and the kinetochore in time and space

2020 ◽  
Vol 64 (2) ◽  
pp. 251-261
Author(s):  
Jessica E. Fellmeth ◽  
Kim S. McKim
Keyword(s):  
Chromosome Segregation ◽  
New Technologies ◽  
Early Prophase ◽  
Unique Role ◽  
Kinetochore Assembly ◽  
M Phase ◽  
In Vivo Analysis ◽  
Meiosis I

Abstract While many of the proteins involved in the mitotic centromere and kinetochore are conserved in meiosis, they often gain a novel function due to the unique needs of homolog segregation during meiosis I (MI). CENP-C is a critical component of the centromere for kinetochore assembly in mitosis. Recent work, however, has highlighted the unique features of meiotic CENP-C. Centromere establishment and stability require CENP-C loading at the centromere for CENP-A function. Pre-meiotic loading of proteins necessary for homolog recombination as well as cohesion also rely on CENP-C, as do the main scaffolding components of the kinetochore. Much of this work relies on new technologies that enable in vivo analysis of meiosis like never before. Here, we strive to highlight the unique role of this highly conserved centromere protein that loads on to centromeres prior to M-phase onset, but continues to perform critical functions through chromosome segregation. CENP-C is not merely a structural link between the centromere and the kinetochore, but also a functional one joining the processes of early prophase homolog synapsis to late metaphase kinetochore assembly and signaling.

TARGETING CYCLIN B1 WITH ANTISENSE OLIGONUCLETOTIDES- COATED SUPERPARAMAGNETIC IRON OXIDE NANOPARTICLES

2018 ◽  
Vol 6 (10) ◽  
Author(s):  
Hosam Zaghloul ◽  
Doaa A. Shahin ◽  
Ibrahim El- Dosoky ◽  
Mahmoud E. El-awady ◽  
Fardous F. El-Senduny ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Iron Oxide Nanoparticles ◽  
Cellular Uptake ◽  
Superparamagnetic Iron Oxide ◽  
Cyclin B1 ◽  
Superparamagnetic Iron Oxide Nanoparticles ◽  
Oxide Nanoparticles ◽  
Mcf7 Cells ◽  
M Phase ◽  
The Impact

Antisense oligonucleotides (ASO) represent an attractive trend as specific targeting molecules but sustain poor cellular uptake meanwhile superparamagnetic iron oxide nanoparticles (SPIONs) offer stability of ASO and improved cellular uptake. In the present work we aimed to functionalize SPIONs with ASO targeting the mRNA of Cyclin B1 which represents a potential cancer target and to explore its anticancer activity. For that purpose, four different SPIONs-ASO conjugates, S-M (1–4), were designated depending on the sequence of ASO and constructed by crosslinking carboxylated SPIONs to amino labeled ASO. The impact of S-M (1–4) on the level of Cyclin B1, cell cycle, ROS and viability of the cells were assessed by flowcytometry. The results showed that S-M3 and S-M4 reduced the level of Cyclin B1 by 35 and 36%, respectively. As a consequence to downregulation of Cyclin B1, MCF7 cells were shown to be arrested at G2/M phase (60.7%). S-M (1–4) led to the induction of ROS formation in comparison to the untreated control cells. Furthermore, S-M (1–4) resulted in an increase in dead cells compared to the untreated cells and SPIONs-treated cells. In conclusion, targeting Cyclin B1 with ASO-coated SPIONs may represent a specific biocompatible anticancer strategy.

The Effects of Butyric Acid on the Differentiation, Proliferation, Apoptosis, and Autophagy of IPEC-J2 Cells

2020 ◽  
Vol 20 (4) ◽  
pp. 307-317
Author(s):  
Yuan Yang ◽  
Jin Huang ◽  
Jianzhong Li ◽  
Huansheng Yang ◽  
Yulong Yin
Keyword(s):  
Cell Viability ◽  
P38 Mapk ◽  
Butyric Acid ◽  
Cell Apoptosis ◽  
Mapk Pathway ◽  
Mrna Level ◽  
Dependent Manner ◽  
M Phase ◽  
High Concentrations ◽  
Underlying Mechanisms

Background: Butyric acid (BT), a short-chain fatty acid, is the preferred colonocyte energy source. The effects of BT on the differentiation, proliferation, and apoptosis of small intestinal epithelial cells of piglets and its underlying mechanisms have not been fully elucidated. Methods: In this study, it was found that 0.2-0.4 mM BT promoted the differentiation of procine jejunal epithelial (IPEC-J2) cells. BT at 0.5 mM or higher concentrations significantly impaired cell viability in a dose- and time-dependent manner. In addition, BT at high concentrations inhibited the IPEC-J2 cell proliferation and induced cell cycle arrest in the G2/M phase. Results: Our results demonstrated that BT triggered IPEC-J2 cell apoptosis via the caspase8-caspase3 pathway accompanied by excess reactive oxygen species (ROS) and TNF-α production. BT at high concentrations inhibited cell autophagy associated with increased lysosome formation. It was found that BT-reduced IPEC-J2 cell viability could be attenuated by p38 MAPK inhibitor SB202190. Moreover, SB202190 attenuated BT-increased p38 MAPK target DDIT3 mRNA level and V-ATPase mRNA level that were responsible for normal acidic lysosomes. Conclusion: In conclusion, 1) at 0.2-0.4 mM, BT promotes the differentiation of IPEC-J2 cells; 2) BT at 0.5 mM or higher concentrations induces cell apoptosis via the p38 MAPK pathway; 3) BT inhibits cells autophagy and promotes lysosome formation at high concentrations.

Titanium Oxide Nanoparticles Improve the Chemotherapeutic Action of Erlotinib in Liver Cancer Cells

2020 ◽  
Vol 16 (4) ◽  
pp. 337-343
Author(s):  
Shaimaa E. Abdel-Ghany ◽  
Eman El-Sayed ◽  
Nour Ashraf ◽  
Nada Mokhtar ◽  
Amany Alqosaibi ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Titanium Oxide ◽  
Phase Distribution ◽  
Oxide Nanoparticles ◽  
Titanium Oxide Nanoparticles ◽  
Liver Cancer Cells ◽  
M Phase ◽  
Apoptosis Detection ◽  
Novel Method

Background: Hepatocellular carcinoma is the second leading cause of cancer-related deaths among other types of cancer due to lack of effective treatments and late diagnosis. Nanocarriers represent a novel method to deliver chemotherapeutic drugs, enhancing their bioavailability and stability. Methods: In the present study, we loaded gold nanoparticles (AuNPs) and titanium oxide nanoparticles (TiO2NPs) with ERL to investigate the efficiency of the formed composite in inducing apoptosis in HepG2 liver cancer cells. Cytotoxicity was assessed using MTT assay and cell phase distribution was assessed by flow cytometry along with apoptosis detection. Results: Data obtained indicated the efficiency of the formed composite to significantly induce cell death and arrest cell cycle and G2/M phase. IRF4 was downregulated after treatment with loaded ERL. Conclusion: Our data showed that loading ERL on TiO2NPs was more efficient than AuNPs. However, both nanocarriers were efficient compared with control.

a Novel Combinational Nanodrug Delivery System Induces Synergistic Inhibition of Lung Adenocarcinoma Cells in vitro

2020 ◽  
Vol 17 ◽  
Author(s):  
Mingliang Fan ◽  
Jiping Li
Keyword(s):  
Lung Adenocarcinoma ◽  
Delivery System ◽  
The Body ◽  
Anticancer Efficacy ◽  
Nanodrug Delivery ◽  
Drug Molecules ◽  
Cellular Assays ◽  
Lung Adenocarcinoma Cell Line ◽  
M Phase

Background: The combination of two or more therapeutic drugs is an attractive approach to improve the treatment of experimental tumors. Leveraging nanocarriers for combinational drug delivery can allow a control over drug biological fate and promote co-localization in the same area of the body. However, there are certain concerns regarding the biodegradability and potential long-term toxicity arising from these synthetic nanoscale carriers. Objective: Our aim was to develop a combinational nanodrug delivery system formed by self-assembling of amphiphilic drug molecules，minimizing potential toxicities associated with using additional synthetic nanocarriers. Methods: A novel prodrug chlorambucil gemcitabine conjugate was synthesized, this prodrug was used for the encapsulation of an additional hydrophobic anticancer drug paclitaxel, taking the form of combinational nanodrugs. Particle size and zeta potential were evaluated, cytotoxicity assay and apoptosis/cell cycle analysis were also performed to validate the anticancer efficacy of the combinational nanodrugs. Results: The combinational nanodrugs were acquired by means of nanoprecipitation. In A549 lung adenocarcinoma cell line, cellular assays revealed that co-delivery of low dosage paclitaxel with chlorambucil gemcitabine conjugate can act synergistically to inhibit cell growth and induce accumulation of cells in the G2/M phase with a concomitant decrease in G0/G1 compartment. Conclusion: Chlorambucil gemcitabine conjugate and paclitaxel can co-assemble into composite nanoparticles by a nanoprecipitation process and the resulting combinational nanodrugs showed synergistic anticancer effect. This synthetic nanocarrier-free approach might broaden the nanodrug concept and have potential in cancer therapy.

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.

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