monastrol has been researched along with Neoplasms* in 9 studies
4 review(s) available for monastrol and Neoplasms
Article | Year |
---|---|
Advances in the discovery of kinesin spindle protein (Eg5) inhibitors as antitumor agents.
Cancer is considered as one of the most serious health problems. Despite the presence of many effective chemotherapeutic agents, their severe side effects together with the appearance of mutant tumors limit the use of these drugs and increase the need for new anticancer agents. Eg5 represents an attractive target for medicinal chemists since Eg5 is overexpressed in many proliferative tissues while almost no Eg5 is detected in nonproliferative tissues. Many Eg5 inhibitors displayed potent anticancer activity against some of the mutant tumors with limited side effects. The present review provides an overview about the progress in the discovery of Eg5 inhibitors especially from 2009 to 2012 as well as the clinical trials conducted on some of these inhibitors. Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Proliferation; Drug Discovery; Humans; Kinesins; Models, Molecular; Molecular Structure; Neoplasms; Structure-Activity Relationship | 2013 |
Never in neutral: a systems biology and evolutionary perspective on how aneuploidy contributes to human diseases.
Whereas germline-inherited whole-chromosome aneuploidy has long been known to cause miscarriages and developmental abnormalities, somatically acquired aneuploidies have been observed in cancer cells and more recently also in cells of the normal liver and brain. Furthermore, aneuploidy is being increasingly reported in clinical isolates of pathogenic microbes such as fungi and parasites. Whereas many efforts have been devoted to the dissection of the molecular mechanisms that lead to aneuploidy, we have only recently started to investigate how aneuploidy alters the phenotypic makeup of a cell. Here we review recent evidence supporting the idea that aneuploidy is a large-effect mutation that introduces large changes in the cellular phenome. From a systems biology perspective, this can be explained by the extensive changes that aneuploidy brings about in both the transcriptome and the proteome of a cell. We further provide an evolutionary perspective on how aneuploidy-induced phenotypic variation may contribute to the exacerbation of human pathologies such as cancer and infectious diseases, by conferring selectable traits such as increased virulence and drug resistance. Topics: Aneuploidy; Animals; Biological Evolution; Chromosomal Instability; Chromosome Segregation; Disease; Humans; Karyotype; Mitosis; Neoplasms; Phenotype; Proteome; Pyrimidines; Stochastic Processes; Systems Biology; Thiones; Transcriptome | 2013 |
Search for new and novel chemotherapeutics for the treatment of human malignancies.
One of the hallmarks of cancer is the uncontrolled cell proliferation which causes more deaths among the human diseases throughout the globe. One in eight deaths worldwide are due to cancer, it is the second and third leading cause of death in economically developed and developing countries, respectively. As it is caused by both external and internal factors, a balanced approach to cancer control includes prevention, early detection, and effective treatment. In the treatment of cancer, chemotherapy is one of the practical methods and is widely used employing drugs that can destroy cancer cells by impeding their growth and reproduction. Despite the great strides made in the treatment of cancer over the past 50 years, it continues to be a major health concern and therefore, extensive efforts have been devoted to search for new scaffolds to develop chemotherapeutics. In this perspective, over the past two decades from this laboratory extensive efforts have been made in the development of new chemotherapeutic agents for the treatment of cancer. In this review, glimpses on types of current chemotherapeutic agents based on their action of inhibition and the new molecules that are being developed based on the scaffolds such as pyrrolo[2,1-c][1,4]benzodiazepines, podophyllotoxins, benzothiadiazine 1,1-dioxides, naphthalimides and monastrol across the world as well as in this laboratory have been articulated. Topics: Antineoplastic Agents; Benzodiazepines; Benzothiadiazines; Humans; Naphthalimides; Neoplasms; Podophyllotoxin; Pyrimidines; Thiones | 2010 |
Progress on kinesin spindle protein inhibitors as anti-cancer agents.
The kinesin spindle protein (KSP, also known as Hs Eg5) plays an essential part in the proper separation of spindle poles and the correct formation of bipolar mitotic spindle during mitosis. Inhibition of this protein results in cells apoptosis followed by mitotic arrest and the formation of characteristic monoaster spindles. Compared with the traditional chemotherapeutic agents (taxanes, vinca alkaloids), KSP inhibitors (KSPi) will not lead to the neuropathic side effects, so KSP has become a novel and an attractive anticancer target. Accordingly, more and more interest has been focused on the development of high effective and selective KSPi. This review will focus on some kinds of KSPi on the basis of introducing structure and function of KSP. Topics: Adenosine Triphosphate; Antineoplastic Agents; Benzamides; Humans; Kinesins; Models, Biological; Models, Molecular; Neoplasms; Pyrimidines; Quinazolines; Spindle Apparatus; Thiones | 2008 |
5 other study(ies) available for monastrol and Neoplasms
Article | Year |
---|---|
Pyrenocine A induces monopolar spindle formation and suppresses proliferation of cancer cells.
Pyrenocine A, a phytotoxin, was found to exhibit cytotoxicity against cancer cells with an IC Topics: Antineoplastic Agents; Cell Cycle Checkpoints; Cell Proliferation; HeLa Cells; Humans; Neoplasms; Pyrimidines; Pyrones; Spindle Apparatus; Thiones | 2019 |
Mitotic slippage and expression of survivin are linked to differential sensitivity of human cancer cell-lines to the Kinesin-5 inhibitor monastrol.
The mitotic Kinesin-5 motor proteins crosslink and slide apart antiparallel spindle microtubules, thus performing essential functions in mitotic spindle dynamics. Specific inhibition of their function by monastrol-like small molecules has been examined in clinical trials as anticancer treatment, with only partial success. Thus, strategies that improve the efficiency of monastrol-like anticancer drugs are required. In the current study, we examined the link between sensitivity to monastrol and occurrence of mitotic slippage in several human cell-lines. We found that the rank of sensitivity to monastrol, from most sensitive to least sensitive, is: AGS > HepG2 > Lovo > Du145 ≥ HT29. We show correlation between the sensitivity of a particular cell-line to monastrol and the tendency of the same cell-line to undergo mitotic slippage. We also found that in the monastrol resistant HT29 cells, prolonged monastrol treatments increase mRNA and protein levels of the chromosomal passenger protein survivin. In contrast, survivin levels are not increased by this treatment in the monastrol-sensitive AGS cells. We further show that over-expression of survivin in the monastrol-sensitive AGS cells reduces mitotic slippage and increases resistance to monastrol. Finally, we show that during short exposure to monastrol, Si RNA silencing of survivin expression reduces cell viability in both AGS and HT29 cells. Our data suggest that the efficiency of anti-cancer treatment with specific kinesin-5 inhibitors may be improved by modulation of expression levels of survivin. Topics: Apoptosis; Blotting, Western; Cell Cycle; Cell Proliferation; Drug Resistance, Neoplasm; Humans; Inhibitor of Apoptosis Proteins; Kinesins; Mitosis; Neoplasms; Pyrimidines; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Small Interfering; Spindle Apparatus; Survivin; Thiones; Tumor Cells, Cultured | 2015 |
Chromosome segregation errors as a cause of DNA damage and structural chromosome aberrations.
Various types of chromosomal aberrations, including numerical (aneuploidy) and structural (e.g., translocations, deletions), are commonly found in human tumors and are linked to tumorigenesis. Aneuploidy is a direct consequence of chromosome segregation errors in mitosis, whereas structural aberrations are caused by improperly repaired DNA breaks. Here, we demonstrate that chromosome segregation errors can also result in structural chromosome aberrations. Chromosomes that missegregate are frequently damaged during cytokinesis, triggering a DNA double-strand break response in the respective daughter cells involving ATM, Chk2, and p53. We show that these double-strand breaks can lead to unbalanced translocations in the daughter cells. Our data show that segregation errors can cause translocations and provide insights into the role of whole-chromosome instability in tumorigenesis. Topics: Ataxia Telangiectasia Mutated Proteins; Cell Cycle Proteins; Cell Line; Cell Line, Tumor; Checkpoint Kinase 2; Chromosomal Instability; Chromosome Aberrations; Chromosome Segregation; Cytokinesis; DNA Breaks, Double-Stranded; DNA-Binding Proteins; Histones; Humans; Intracellular Signaling Peptides and Proteins; Neoplasms; Phosphorylation; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Protein-Tyrosine Kinases; Pyrimidines; Thiones; Translocation, Genetic; Tumor Suppressor p53-Binding Protein 1; Tumor Suppressor Protein p53; Tumor Suppressor Proteins | 2011 |
Design and in vitro evaluation of branched peptide conjugates: turning nonspecific cytotoxic drugs into tumor-selective agents.
The use of peptide receptors as targets for tumor-selective therapies was envisaged years ago with the findings that receptors for different endogenous regulatory peptides are overexpressed in several primary and metastatic human tumors, and can be used as tumor antigens. Branched peptides can retain or even increase, through multivalent binding, the biological activity of a peptide and are very resistant to proteolysis, thus having a markedly higher in vivo activity compared with the corresponding monomeric peptides. Oligo-branched peptides, containing the human regulatory peptide neurotensin (NT) sequence, have been used as tumor-specific targeting agents. These peptides are able to selectively and specifically deliver effector units, for cell imaging or killing, to tumor cells that overexpress NT receptors. Results obtained with branched NT conjugated to different functional units for tumor imaging and therapy indicate that branched peptides are promising novel multifunctional targeting molecules. This study is focused on the role of the releasing pattern of drug-conjugated branched NT peptides. We present results obtained with oligo-branched neurotensin peptides conjugated to 6-mercaptopurin (6-MP), combretastain A-4 (CA4) and monastrol (MON). Drugs were conjugated to oligo-branched neurotensin through different linkers, and the mode-of-release, together with cytotoxicity, was studied in different human cancer cell lines. The results show that branched peptides are very promising pharmacodelivery options. Among our drug-armed branched peptides, NT4-CA4 was identified as a candidate for further development and evaluation in preclinical pharmacokinetic and pharmacodynamic studies. This peptide-drug exhibits significant activity against pancreas and prostate human cancer cells. Consequently, this derivative is of considerable interest due to the high mortality rates of pancreas neuroendocrine tumors and the high incidence of prostate cancer. Topics: Antineoplastic Agents; Drug Design; Drug Evaluation, Preclinical; Drug Screening Assays, Antitumor; Humans; Mercaptopurine; Neoplasms; Neurotensin; Peptides; Pyrimidines; Receptors, Neurotensin; Stilbenes; Thiones | 2010 |
Chemical genetics reveals a complex functional ground state of neural stem cells.
The identification of self-renewing and multipotent neural stem cells (NSCs) in the mammalian brain holds promise for the treatment of neurological diseases and has yielded new insight into brain cancer. However, the complete repertoire of signaling pathways that governs the proliferation and self-renewal of NSCs, which we refer to as the 'ground state', remains largely uncharacterized. Although the candidate gene approach has uncovered vital pathways in NSC biology, so far only a few highly studied pathways have been investigated. Based on the intimate relationship between NSC self-renewal and neurosphere proliferation, we undertook a chemical genetic screen for inhibitors of neurosphere proliferation in order to probe the operational circuitry of the NSC. The screen recovered small molecules known to affect neurotransmission pathways previously thought to operate primarily in the mature central nervous system; these compounds also had potent inhibitory effects on cultures enriched for brain cancer stem cells. These results suggest that clinically approved neuromodulators may remodel the mature central nervous system and find application in the treatment of brain cancer. Topics: Animals; Cell Survival; Cells, Cultured; Mice; Molecular Structure; Neoplasms; Neurons; Pharmaceutical Preparations; Sensitivity and Specificity; Stem Cells | 2007 |