Aim: The mitotic spindle plays a key role in cell division which makes it an important target in cancer therapy. In the present study the antiproliferative activity of 4-benzyl-5-phenyl-3,4-dihydropyrimidine-2(1H)-thione (1) and its pyridine bioisoster (2) were evaluated and compared with monastrol (MON), the first known cell-permeable small molecule which disrupts bipolar spindle formation by inhibiting Eg5-kinesin activity.
Results: Our data revealed that compound 2 showed higher antiproliferative activity than MON against MCF7 and A375 cell lines and comparable reversible cell cycle inhibition in G2/M phase. However, compound 2 produced distinct phenotype from monoastral spindles, and did not affect Eg5 ATPase activity.
Conclusion: The activity of compound 2 may suggest its new promising anticancer mechanism (different than MON), targeting other component required for spindle bipolarity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.4155/fmc-2018-0094 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Insights into NEK2 inhibitors as antitumor agents: From mechanisms to potential therapeutics.
Eur J Med Chem
January 2025
Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Healthand, Department of Frontiers Science Center for Disease-related Molecular Network, Core Facilities, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. Electronic address:
NEK2, a serine/threonine protein kinase, is integral to mitotic events such as centrosome duplication and separation, microtubule stabilization, spindle assembly checkpoint, and kinetochore attachment. However, NEK2 overexpression leads to centrosome amplification and chromosomal instability, which are significantly associated with various malignancies, including liver, breast, and non-small cell lung cancer. This overexpression could facilitate tumor development and confer resistance to therapy by promoting aberrant cell division and centrosome amplification.
View Article and Find Full Text PDFTo direct regulated protein degradation, the 26S proteasome recognizes ubiquitinated substrates through its 19S particle and then degrades them in the 20S enzymatic core. Despite this close interdependency between proteasome subunits, we demonstrate that knockouts from different proteasome subcomplexes result in distinct highly cellular phenotypes. In particular, depletion of 19S PSMD lid proteins, but not that of other proteasome subunits, prevents bipolar spindle assembly during mitosis, resulting in a mitotic arrest.
View Article and Find Full Text PDFNon-Myxoid Solid Variant of Extraskeletal Myxoid Chondrosarcoma: An Underrecognized Subtype.
Hum Pathol
January 2025
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address:
Introduction: Extraskeletal myxoid chondrosarcoma (EMC) is a rare sarcoma defined by NR4A3 gene rearrangements, typically featuring uniform cells with eosinophilic cytoplasm and mild atypia, arranged in cords or clusters within a chondromyxoid stroma. A cellular variant, characterized by increased cellular density and a solid growth pattern, has been recognized.
Methods: We encountered three cases of round cell sarcomas, diagnosed as EMC based on NR4A3 or NR4A2 rearrangements.
NME7 maintains primary cilium assembly, ciliary microtubule stability, and Hedgehog signaling.
Life Sci Alliance
April 2025
https://ror.org/0040axw97 Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, China
NME7 (nucleoside diphosphate kinase 7), a lesser studied member of the non-metastatic expressed (NME) family, has been reported as a potential subunit of the γ-tubulin ring complex (γTuRC). However, its role in the cilium assembly and function remains unclear. Our research demonstrated that NME7 is located at the centrosome, including at the spindle poles during metaphase and at the basal bodies during cilium assembly.
View Article and Find Full Text PDFPathological Spectrum of Melanoma: A Nine-Year Retrospective Analysis of Tumor Characteristics Across Diverse Anatomic Sites.
Cureus
December 2024
Ophthalmology, All India Institute of Medical Sciences, Madurai, Madurai, IND.
Melanoma is a highly aggressive malignancy originating from melanocytes, characterized by its potential to arise in various anatomic locations, both common and rare. The incidence of melanoma has been steadily increasing globally, with variations in clinical presentation, tumor behavior, and prognosis depending on the anatomical site involved. Understanding the diverse pathological spectrum of melanoma is critical for optimizing diagnostic and therapeutic strategies.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!