BACKGROUND Farnesyltransferase inhibitors have the ability to interfere with various intracellular pathways, reducing cell survival and proliferation. They have become an attractive tool for cancer therapy, namely acute leukemias. In this work, we have studied the efficacy of α-hydroxyfarnesylphosphonic acid (α-HFPA) in CEM (acute T-cell lymphoblastic leukemia) in culture. MATERIALS AND METHO...

Targeting topoisomerase II (topo II) is regarded as an important component of the pleiotropic mechanism of action of anthracycline drugs. Here, we show that 4-demethoxy analogues of doxorubicin, including annamycin, exhibit a greater ability to trap topo II cleavage complexes than doxorubicin and some other 4-methoxy analogues. In leukemic CEM cells with wild-type topo II, annamycin induced sub...

Laxaphycin A (laxa A) and Laxaphycin B (laxa B), cyclic peptides isolated from the terrestrial blue-green alga Anabaena laxa or the marine cyanobacterium Lyngbya majuscula have antifungal and cytotoxic activities. We used numerical videomicrofluorometry and a protocol of multiple labelling with Hoescht 33342 (nuclear DNA), Rhodamine 123 (mitochondria) and Nile Red (plasma membrane) to study the...

The HIV-1 Vif protein suppresses the inhibition of viral replication caused by the human antiretroviral factor APOBEC3G. As a result, HIV-1 mutants that do not express the Vif protein are replication incompetent in 'nonpermissive' cells, such as primary T cells and the T-cell line CEM, that express APOBEC3G. In contrast, Vif-defective HIV-1 replicates effectively in 'permissive' cell lines, suc...

PR-924 is a novel prototypic immunoproteasome inhibitor bearing markedly enhanced specificity for the β5i immunoproteasome subunit, compared to the classical proteasome inhibitor bortezomib. Here, we assessed the growth inhibitory potential of PR-924 in three human hematologic malignancy cell lines (CCRF-CEM, THP1, and 8226) and their bortezomib-resistant sublines. Parental cells displayed equa...

Nelarabine, prodrug of arabinosylguanine (ara-G), has demonstrated T-lymphoblastic antileukemic activity in cell lines and in the clinic. To investigate the mechanism for lineage-specific toxicity, the effects of ara-G were compared in CEM (T-lymphoblast), Raji (B-lymphoblast), and ML-1 (myeloid) cell lines. CEM cells were the most sensitive to ara-G-induced apoptosis and accumulated the highes...

Recent studies suggest that the generation of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) or superoxide (O2-) may play a role in monocyte antibody-dependent cytotoxicity (ADCC). We studied ADCC by normal human monocytes, and monocytes from chronic granulomatous disease (CGD) patients, cells unable to generate ROS, toward anti-D sensitized human red cells (RBC) and an antibody...

DNA topoisomerase (topo) IIalpha gene expression or activity is altered in tumor cells selected for resistance to inhibitors of topoII. To better understand the mechanisms by which topoIIalpha expression levels are modulated, we examined topoIIalpha transcriptional regulation in ICRF-187-sensitive and ICRF-187-resistant human leukemic cell lines that express an increased amount of topoIIalpha p...

introduction: the tumor suppressor p53 protein can induce apoptosis in some cellular contexts. among the apoptosis-inducing genes, p53 has received the most attention for cancer gene therapy. in this study, the role of dendrosome and lipofectin mediated normal cdna of tp53 into molt-4, ccrf-cem(t-iymphoma) and k562 cell lines was assessed. material and methods: at first, ccrf-cem, mol t-4 and k...

The human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs)-saquinavir, ritonavir, nelfinavir, and indinavir-interact with the ABC-type multidrug transporter proteins MDR1 and MRP1 in CEM T-lymphocytic cell lines. Calcein fluorescence was significantly enhanced in MDR1(+) CEM/VBL100 and MRP1(+) CEM/VM-1-5 cells incubated in the presence of various HIV PIs and calcein acetoxymethyl...