The DNA topoisomerase IIalpha (Topo IIalpha) is known as a target enzyme for many chemotherapeutic agents. We investigated the Topo IIalpha mRNA expression by real-time RT-PCR in 37 paired samples at diagnosis and at relapse of acute leukemic patients in relation to drug sensitivity and clinical outcome. The Topo IIalpha levels in leukemic blasts at relapse were significantly higher than that at diagnosis, especially in ALL. The increase in the Topo IIalpha level at relapse was significant in cases which could not achieve a second remission, but not significant in cases which achieved a second remission. These results suggest that the change of Topo IIalpha expression in leukemic blasts at relapse may predict therapeutic responsiveness.
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http://dx.doi.org/10.1016/j.leukres.2008.12.012 | DOI Listing |
BMC Complement Med Ther
November 2024
Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt.
Background: Fagonia cretica L. (Family: Zygophyllaceae), is a wild shrub mostly found in Mediterranean districts and extensively used in folk medicine for a vast array of purposes such as antidiabetic and anticancer during the early stages. The goal of the current study was to validate the antioxidant, anti-inflammatory, and cytotoxic properties of Egyptian F.
View Article and Find Full Text PDFbioRxiv
October 2024
Department of Physics & LASSP, Cornell University, Ithaca, NY 14853, USA.
Topoisomerase II (topo II) enzymes are essential enzymes known to resolve topological entanglements during DNA processing. Curiously, while yeast expresses a single topo II, humans express two topo II isozymes, topo IIα and topo IIβ, which share a similar catalytic domain but differ in their intrinsically disordered C-terminal domains (CTDs). During mitosis, topo IIα and condensin I constitute the most abundant chromosome scaffolding proteins essential for chromosome condensation.
View Article and Find Full Text PDFFood Chem
February 2025
State Key Laboratory of Food Science and Technology, School of Food Science and Technology, National Engineering Research Center for Functional Food, Jiangnan University, 1800 Lihu Avenue, Wuxi 214122, China. Electronic address:
This study investigates the potential of germinated black bean extracts (GBBE) to modulate the activity of topoisomerase IIα (topo IIα), a key enzyme involved in DNA replication and repair, particularly in triple-negative breast cancer (TNBC). Germination significantly elevated the polyphenolic content of black beans, thereby enhancing their antioxidant properties. Molecular docking studies demonstrated a strong interaction between GBBE and the active site of topo IIα, suggesting a possible mechanism for its inhibitory action.
View Article and Find Full Text PDFComput Struct Biotechnol J
December 2024
National Institute of Chemistry, Hajdrihova 19, SI 1000 Ljubljana, Slovenia.
The 4,6-substituted-1,3,5-triazin-2(1)-ones are promising inhibitors of human DNA topoisomerase IIα. To further develop this chemical class targeting the enzyme´s ATP binding site, the triazin-2(1)-one substitution position 6 was optimized. Inspired by binding of preclinical substituted 9-purine derivative, bicyclic substituents were incorporated at position 6 and the utility of this modification was validated by a combination of molecular simulations, dynamic pharmacophores, and free energy calculations.
View Article and Find Full Text PDFChem Biol Drug Des
July 2024
División de Ciencias Naturales y Exactas, Departamento de Química, Universidad de Guanajuato, Guanajuato, Mexico.
We have conducted an experimental and computational evaluation of new doxorubicin (4a-c) and β-lapachone (5a-c) analogs. These novel anticancer analogs were previously synthesized, but had not been tested or characterized until now. We have evaluated their antiproliferative and DNA cleavage inhibition properties using breast (MCF-7 and MDA-MB-231) and prostate (PC3) cancer cell lines.
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