The aim of the study was to determine the relation between the cytotoxic and cytostatic effects of tezacitabine and cladribine on a HL-60 cell line and the time of exposure of cells to these drugs. Cell viability and induction of apoptosis were assessed using flow cytometry methods. Apoptosis was confirmed by direct microscopic observation. Growth inhibition was examined by cell counting. After 24 h incubation tezacitabine was equally or less toxic compared to cladribine. However, toxicity of tezacitabine strongly rose after 48 h incubation leading to massive cell death at doses much lower than those of cladribine. Assessment of the effect of increased exposure time on the clinical efficacy of tezacitabine is indicated.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
Clinical pharmacology and clinical trials of ribonucleotide reductase inhibitors: is it a viable cancer therapy?
J Cancer Res Clin Oncol
August 2017
Department of Biopharmaceutical Sciences, Roosevelt University College of Pharmacy, 1400 N. Roosevelt Blvd., Schaumburg, IL, 60173, USA.
Purpose: Ribonucleotide reductase (RR) enzymes (RR1 and RR2) play an important role in the reduction of ribonucleotides to deoxyribonucleotides which is involved in DNA replication and repair. Augmented RR activity has been ascribed to uncontrolled cell growth and tumorigenic transformation.
Methods: This review mainly focuses on several biological and chemical RR inhibitors (e.
Tezacitabine enhances the DNA-directed effects of fluoropyrimidines in human colon cancer cells and tumor xenografts.
Biochem Pharmacol
January 2007
Department of Pharmacology, Chiron Corporation, Emeryville, CA 94608, United States.
Tezacitabine is a nucleoside analogue characterized by a dual mechanism of action. Following intracellular phosphorylation, the tezacitabine diphosphate irreversibly inhibits ribonucleotide reductase, while the tezacitabine triphosphate can be incorporated into DNA during replication or repair, resulting in DNA chain termination. In the present study we have investigated the effect of the combination of tezacitabine and 5-fluorouracil (5-FU) or 5-fluoro-2'-deoxyuridine (FUdR) on HCT 116 human colon carcinoma cells and xenografts.
View Article and Find Full Text PDFTezacitabine blocks tumor cells in G1 and S phases of the cell cycle and induces apoptotic cell death.
Acta Pol Pharm
October 2005
Flow Cytometry Laboratory, The National Institute of Public Health, 30/34 Chełmska Str, 00-725 Warsaw, Poland.
Tezacitabine (FMdC) is a new cytostatic/cytotoxic agent widely investigated in clinical trials and on the cellular level. In a previous paper (3) we worked on human and murine leukemia (L-1210, HL-60, and MOLT-4) cells, and in this paper we investigated the influence of FMdC on the cell cycle and apoptosis in vitro of three other leukemias (CCRF-SB, KG-1, and Jurkat), and human solid tumor (carcinoma) cell lines (COLO-205, MCF-7, and PC-3). We found that FMdC induces the G1 (at concentrations higher than 10 nM).
View Article and Find Full Text PDFCytotoxic effects of cladribine and tezacitabine toward HL-60.
Acta Biochim Pol
August 2009
Flow Cytometry Laboratory, National Institute of Public Health, Warszawa, Poland.
The aim of the study was to determine the relation between the cytotoxic and cytostatic effects of tezacitabine and cladribine on a HL-60 cell line and the time of exposure of cells to these drugs. Cell viability and induction of apoptosis were assessed using flow cytometry methods. Apoptosis was confirmed by direct microscopic observation.
View Article and Find Full Text PDFPhase I dose-escalation study of tezacitabine in combination with 5-fluorouracil in patients with advanced solid tumors.
Cancer
May 2005
Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Background: Tezacitabine [(E)-2'-deoxy-2'-(fluoromethylene) cytidine; FMdC] is a novel nucleoside analog with potent antiproliferative and antitumor activity in preclinical studies. A tolerable safety profile and clinical activity have been shown in Phase I and Phase II clinical studies. The purpose of the current open-label, Phase I dose-escalation trial was to evaluate the combination of tezacitabine and 5-fluorouracil (5-FU) in the treatment of patients with advanced solid tumors.
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!