On Centrioles, Microtubules, and Cellular Electromagnetism

Author(s):  
Ronald L. Huston

This paper describes the inner workings of centrioles (a pair of small organelles adjacent to the nucleus) as they create cell electropolarity, engage in cell division (mitosis), but in going awry, also promote the development of cancers. The electropolarity arises from vibrations of microtubules composing the centrioles. Mitosis begins as each centrioles duplicates itself by growing a daughter centriole on its side. If during duplication more than one daughter is grown, cancer can occur and the cells divide uncontrollably. Cancer cells with supernumerary centrioles have high electropolarity which can serve as an attractor for charged therapeutic nanoparticles.

2013 ◽  
Vol 4 (6) ◽  
pp. 447-457 ◽  
Author(s):  
Hong-Wu Xin ◽  
Chenwi M. Ambe ◽  
Satyajit Ray ◽  
Bo-Kyu Kim ◽  
Tomotake Koizumi ◽  
...  

2020 ◽  
Author(s):  
Maria ◽  
Zahid Khan

AbstractComputational approaches have emerging role for designing potential inhibitors against topoisomerase 2 for treatment of cancer. TOP2A plays a key role in DNA replication before cell division and thus facilitates the growth of cells. This function of TOP2A can be suppressed by targeting with potential inhibitors in cancer cells to stop the uncontrolled cell division. Among potential inhibitors cryptolepine is more selective and has the ability to intercalate into DNA, effectively block TOP2A and cease cell division in cancer cells. However, cryptolepine is non-specific and have low affinity, therefore, a combinatorial library was designed and virtually screened for identification of its derivatives with greater TOP2A binding affinities.A combinatorial library of 31114 derivatives of cryptolepine was formed and the library was virtually screened by molecular docking to predict the molecular interactions between cryptolepine derivatives and TOP2A taking cryptolepine as standard. The overall screening and docking approach explored all the binding poses of cryptolepine for TOP2A to calculate binding energy. The compounds are given database number 8618, 907, 147, 16755, and 8186 scored lowest binding energies of −9.88kcal/mol, −9.76kcal/mol, −9.75kcal/mol, −9.73kcal/mol, and −9.72kcal/mol respectively and highest binding affinity while cryptolepine binding energy is −6.09kcal/mol. The good binding interactions of the derivatives showed that they can be used as potent TOP2A inhibitors and act as more effective anticancer agents than cryptolepine itself. The interactions of derivatives with different amino acid residues were also observed. A comprehensive understanding of the interactions of proposed derivatives with TOP2A helped for searching more novel and potent drug-like molecules for anticancer therapy. This Computational study suggests useful references to understand inhibition mechanisms that will help in the modification of TOP2A inhibitors.


2000 ◽  
Vol 20 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Maria E. Mycielska ◽  
Monika Schäfer ◽  
Scott P. Fraser ◽  
Mustafa B. A. Djamgoz ◽  
C. Lindsay Bashford

A study was initiated to test whether the FM1–43 dye technique could beapplied to the study of endocytic membrane activity in two rodent prostatecancer (MAT-LyLu and AT-2) cell lines of markedly different metastaticability. The lipophilic dye FM1–43, which has frequently been used tomonitor endo/exocytic activity in excitable cells was employed. We found,as in excitable tissues, that both strongly metastatic (MAT-LyLu) andweakly metastatic (AT-2) cells in culture take up FM1–43 to give vesicularstaining of a variable pattern, which appeared to differ between the twocell lines. However, unlike excitable tissues, neither cell linesubsequently released the dye. Indeed, both cell lines retained the dyethrough several rounds of cell division suggesting that dye incorporatedby cells does not enter the endo/exocytotic cycle. Uptake of dye wasindependent of temperature, Na+/K+ gradients, pH or metabolism. Wesuggest that passive accumulation of FM1–43 can occur in cancer cells andshould not, automatically, be interpreted as evidence of endocytosis.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Dan Zhang ◽  
Yijia Wang ◽  
Shiwu Zhang

Asymmetric cell division is critical for generating cell diversity in low eukaryotic organisms. We previously have reported that polyploid giant cancer cells (PGCCs) induced by cobalt chloride demonstrate the ability to use an evolutionarily conserved process for renewal and fast reproduction, which is normally confined to simpler organisms. The budding yeast,Saccharomyces cerevisiae, which reproduces by asymmetric cell division, has long been a model for asymmetric cell division studies. PGCCs produce daughter cells asymmetrically in a manner similar to yeast, in that both use budding for cell polarization and cytokinesis. Here, we review the results of recent studies and discuss the similarities in the budding process between yeast and PGCCs.


PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0162633 ◽  
Author(s):  
Yue He ◽  
Daoyu Yan ◽  
Dianpeng Zheng ◽  
Zhiming Hu ◽  
Hongwei Li ◽  
...  

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1698 ◽  
Author(s):  
Sambi ◽  
DeCarlo ◽  
Malardier-Jugroot ◽  
Szewczuk

Nanomedicine as a multimodality treatment of cancer utilizes the advantages of nanodelivery systems of drugs. They are superior to the clinical administration of different therapeutic agents in several aspects, including simultaneous delivery of drugs to the active site, precise ratio control of the loading drugs and overcoming multidrug resistance. The role of nanopolymer size and structural shape on the internalization process and subsequent intracellular toxicity is limited. Here, the size and shape dependent mechanism of a functionalized copolymer was investigated using folic acid (FA) covalently bonded to the copolymer poly (styrene-alt-maleic anhydride) (SMA) on its hydrophilic exterior via a biological linker 2,4-diaminobutyric acid (DABA) to target folic acid receptors (FR) overly expressed on cancer cells actively. We recently reported that unloaded FA-DABA-SMA copolymers significantly reduced cancer cell viability, suggesting a secondary therapeutic mechanism of action of the copolymer carrier post-internalization. Here, we investigated the size and shape dependent secondary mechanism of unloaded 350 kDa and 20 kDa FA-DABA-SMA. The 350 kDa and 20 kDa copolymers actively target folic acid receptors (FR) to initialize internationalization, but only the large size and sheet shaped copolymer disables cell division by intracellular disruptions of essential oncogenic proteins including p53, STAT-3 and c-Myc. Furthermore, the 350 kDa FA-DABA-SMA activates early and late apoptotic events in both PANC-1 and MDA-MB-231 cancer cells. These findings indicate that the large size and structural sheet shape of the 350 kDa FA-DABA-SMA copolymer facilitate multimodal tumor targeting mechanisms together with the ability to internalize hydrophobic chemotherapeutics to disable critical oncogenic proteins controlling cell division and to induce apoptosis. The significance of these novel findings reveals copolymer secondary cellular targets and therapeutic actions that extend beyond the direct delivery of chemotherapeutics. This report offers novel therapeutic insight into the intracellular activity of copolymers critically dependent on the size and structural shape of the nanopolymers.


Nutrients ◽  
2017 ◽  
Vol 9 (2) ◽  
pp. 109 ◽  
Author(s):  
Yu Zhang ◽  
Ying-bo Xue ◽  
Hang Li ◽  
Dong Qiu ◽  
Zhi-wei Wang ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Mugahed Abdullah Hasan Albahde ◽  
Bulat Abdrakhimov ◽  
Guo-Qi Li ◽  
Xiaohu Zhou ◽  
Dongkai Zhou ◽  
...  

Pancreatic cancer has an extremely low prognosis, which is attributable to its high aggressiveness, invasiveness, late diagnosis, and lack of effective therapies. Among all the drugs joining the fight against this type of cancer, microtubule-targeting agents are considered to be the most promising. They inhibit cancer cells although through different mechanisms such as blocking cell division, apoptosis induction, etc. Hereby, we review the functions of microtubule cytoskeletal proteins in tumor cells and comprehensively examine the effects of microtubule-targeting agents on pancreatic carcinoma.


2020 ◽  
Author(s):  
Rajnish Kumar Singh ◽  
Yonggang Pei ◽  
Zachary L Lamplugh ◽  
Kunfeng Sun ◽  
Yan Yuan ◽  
...  

AbstractThe cellular adaptive response to hypoxia, mediated by high HIF1α levels includes metabolic reprogramming, restricted DNA replication and cell division. In contrast to healthy cells, the genome of cancer cells, and Kaposi’s sarcoma associated herpesvirus (KSHV) infected cells maintains replication in hypoxia. We show that KSHV infection, despite promoting expression of HIF1α in normoxia, can also restricts transcriptional activity, and promoted its degradation in hypoxia. KSHV-encoded vCyclin, expressed in hypoxia, mediated HIF1a cytosolic translocation, and its degradation through a non-canonical lysosomal pathway. Attenuation of HIF1α levels by vCyclin allowed cells to bypass the block to DNA replication and cell proliferation in the hypoxia. These results demonstrated that KSHV utilizes a unique strategy to balance HIF1α levels to overcome replication arrest and induction of the oncogenic phenotype, which are dependent on the levels of oxygen in the microenvironment.


2019 ◽  
Author(s):  
Ting Wang ◽  
Yiqian Liang ◽  
Asmitananda Thakur

Abstract Background S100 calcium binding protein A2 (S100A2) has been confirmed to have an abnormal expression in lung cancer and is associated with a better disease-free internal of lung cancer patients. Our previous studies on S100A2 in lung cancer concentrated on the clinical roles of this protein in lung cancer, finding that S100A2 increasingly expressed in the sera, tissues and plural effusion of lung cancer patients. This study emphasizes its value in the lung cancer cell line.Methods We constructed a S100A2 expression lentivirus vector, then transfected it and blank vector into the Calu-6 lung cancer cell line respectively. After the successful transfection, (which was confirmed by RT-PCR and Western-blot), we used MTT, transwell and flow cytometric analysis to compare the differences in cell proliferation, cell migration, cell invasion, cell apoptosis and cell cycle among the three groups (Calu-6, Calu/neo, Calu-6/S100A2).Results Calu-6 lung cancer cells showed a shift from G1 to S phase after being transfected with S100A2, compared with the control groups. Additionally, Calu-6/S1000A2 cells had enhanced abilities of invasion and down-abilities of apoptosis in contrast with the blank groups (P<0.05). However, there were no significant difference among these three group in the cell behaviors of migration and proliferation (P>0.05).Conclusion Our results firstly indicate that S100A2 has a positive influence on the biological characteristics of Calu-6 lung cancer cell line, including cell division, invasion and apoptosis inhibition. It may play a significant role in the genesis and progression of lung cancer.


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