Abstract:
:We have previously synthesized various diazenecarboxamides (subsequently referred to as diazenes) that were cytotoxic to several tumor cell lines. To increase their biological activity, the structure has been modified appropriately. In the present study we examined the effects of N(1)-phenyl-N(2)-(2-pyridinylmethyl)diazenedicarboxamide (RL-337) obtained from the previously examined cytotoxic compound N(1)-phenyl-N(2)-(2-pyridinyl)diazenecarboxamide (JK-279), and compared them with those of diazene JK-279. Using a modified colorimetric MTT assay, the cytotoxicity of RL-337 was determined on human cervical carcinoma HeLa cells, glioblastoma A1235 cells, and prostate adenocarcinoma PC-3 cells. The possible synergistic effect of diazene RL-337 with cisplatin, doxorubicin, and vincristine, and its influence on intracellular GSH content was examined on HeLa cells. Diazene RL-337 was cytotoxic against all three human tumor cell lines, being more cytotoxic to HeLa cells than diazene JK-279. The higher efficacy of RL-337 than of JK-279 can be connected with higher basicity of the 2-picoline moiety present in the former diazene comparing with the pyridine fragment that is a part of the latter. The diazene RL-337 acted synergistically with cisplatin, doxorubicin, and vincristine (diazene JK-279 exhibited synergistic effect only with cisplatin). Glutathione (determined by Tietze's method) was not a target molecule of diazene RL-337 (but was for JK-279, as shown earlier). After just 1 h treatment with diazene RL-337, the cells started to lose membrane integrity. There was no cleavage of caspase-3 in RL-337-treated samples, and the majority of cells died 6 h after the treatment through necrosis (previously, apoptosis-like cell death was detected for diazene JK-279). Thus, although diazenes JK-279 and RL-337 are very similar in their structure, they exhibit widely different biological activity.
journal_name
Cell Biol Toxicoljournal_title
Cell biology and toxicologyauthors
Jakopec S,Dubravcic K,Brozovic A,Polanc S,Osmak Mdoi
10.1007/s10565-006-0023-2subject
Has Abstractpub_date
2006-01-01 00:00:00pages
61-71issue
1eissn
0742-2091issn
1573-6822journal_volume
22pub_type
杂志文章abstract::A method for the primary culture of rat liver cells on collagen-coated dextran microcarriers is described. Ethoxycoumarin deethylase (EOD) activity 24 hr after inoculation was comparable for liver cells cultured on microcarriers and on collagen-coated dishes. Cells were cultured on microcarriers for up to 48 hr and re...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/BF00124073
更新日期:1991-10-01 00:00:00
abstract::Clinical tests of gene sequence, structure, and function are to predict, diagnose, monitor, and prognose human disease-specific phenomes, characters severities, durations, stages, and responses to therapy. The concept and content of gene tests for clinical application mainly include chromosome/chromatins, DNA, and RNA...
journal_title:Cell biology and toxicology
pub_type: 社论
doi:10.1007/s10565-019-09464-w
更新日期:2019-04-01 00:00:00
abstract::Based on the reduced expression of ethanol-oxidizing enzymes in human hepatocellular carcinoma (HepG2) cells, we analyzed the role of nonoxidative metabolites in ethanol-induced apoptosis in HepG2 cells. For this purpose, an analysis of volatile metabolites of ethanol using ion-mobility spectrometry and gas chromatogr...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-007-9009-y
更新日期:2007-11-01 00:00:00
abstract::Cd2+ provokes inositol trisphosphate production and releases stored Ca2+, apparently by binding to a zinc site in the external domain of an orphan receptor. One microM Cd2+ evokes an immediate spike in cytosolic free Ca2+, which is similar to that evoked by bradykinin. Platelet-derived growth factor (PDGF) also increa...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/BF00757576
更新日期:1993-04-01 00:00:00
abstract::The mechanism by which lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA) induces production of proinflammatory cytokines in murine macrophages, and the role of phosphatidylinositol 3-kinase (PI3-kinase) have not been well investigated. Activation of nuclear factor kappaB (NF-kappaB) is initiated by the...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1023/a:1015384201785
更新日期:2002-01-01 00:00:00
abstract::In a number of adverse drug reactions leading to hepatotoxicity drug metabolism is thought to be involved by generation of reactive metabolites from nontoxic drugs. In this study, an in vitro assay was developed for measurement of the impact of metabolic activation of compound on the cytotoxicity toward a human hepati...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-007-9018-x
更新日期:2008-01-01 00:00:00
abstract::The effects of the oxidizing agent t-butylhydroperoxide (t-BHP) were investigated on three human cell lines of different origin and growth features (A431 epithelial cells, ADF astrocytoma cells and U937 leukemic cells) using electron microscopy and electron paramagnetic resonance spectroscopy. The results indicate tha...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/BF00756761
更新日期:1994-08-01 00:00:00
abstract::The piperidine nitroxides Tempamine and Tempace have been studied for their effect on doxorubicin (DOX) and hydrogen peroxide (H(2)O(2)) cytotoxicity in immortalized B14 cells, a model for neoplastic phenotype. The significance for nitroxide performance of the substituent in position 4 of the piperidine ring was evalu...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-007-9020-3
更新日期:2008-01-01 00:00:00
abstract::Many of the differentiated functions of hepatocytes are lost in culture, yet addition of certain medium supplements can aid in the retention of differentiated character. Therefore, the effect of time in monolayer culture on rat hepatocyte glutathione (GSH) synthesis and sensitivity to the GSH detoxicated xenobiotic et...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/BF00117851
更新日期:1986-12-01 00:00:00
abstract::Glioblastoma (GBM) is the most aggressive type of glioma. Temozolomide (TMZ) is currently the drug of choice used for post-operative chemotherapy of GBM. However, the presence of intrinsic and acquired resistance hinders the success of chemotherapy. To understand the TMZ resistant mechanisms in glioma, we investigated...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-019-09502-7
更新日期:2020-06-01 00:00:00
abstract::DNA methylation is catalyzed by a family of DNA methyltransferases (DNMTs) including the maintenance enzyme DNMT 1 and de novo methyltransferases DNMT 3a and DNMT 3b. Elevated levels of DNMTs have been found in cancer cells and in several types of human tumors. A polymorphism found in DNMT3b has been associated with i...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-007-9035-9
更新日期:2008-06-01 00:00:00
abstract::Two human hepatoma cell lines, KYN-2 and Mz-Hep-1 were characterized in terms of glucuronidation capacity and inducibility of cytochrome P4501A1/1A2 and several UDP-glucuronosyltransferases (UGTs). Cytochrome P4501A1/1A2 activity was measured using 7-ethoxyresorufin and that of UGTs with 16 different substrates. The e...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/BF00143361
更新日期:1996-04-01 00:00:00
abstract::Asiatic acid (AA), a triterpene, is known to be cytotoxic to several tumor cell lines. AA induces dose- and time-dependent cell death in U-87 MG human glioblastoma. This cell death occurs via both apoptosis and necrosis. The effect of AA may be cell type-specific as AA-induced cell death was mainly apoptotic in colon ...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-006-0104-2
更新日期:2006-11-01 00:00:00
abstract::Metolachlor, a commonly used herbicide in the Midwestern USA, functions by inhibiting chlorophyll and protein synthesis in target plants. Herbicide exposure has led to detrimental effects in several organisms, affecting their growth and behavior; however, its mechanism of action in nontarget organisms is not yet clear...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-013-9256-z
更新日期:2013-08-01 00:00:00
abstract::Considering the recent studies that question previously reported cardio-protective effects of estrogen, there is a growing concern that endocrine disruptors may also contribute to the pathology of cardiovascular disease. PCB153 is one of the most commonly found polychlorinated biphenyls, and based on epidemiological s...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-010-9170-6
更新日期:2011-02-01 00:00:00
abstract::To determine the toxicological effects of complex mixtures of pesticides, we obtained data on 100 pesticide residues in common foods of central Italy. Fifteen pesticides were more regularly detected at higher levels (dithiocarbamates, benomyl/carbendazim, thiabendazole, diphenylamine, chlorthalonil, procymidone, fenar...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/BF00754461
更新日期:1993-10-01 00:00:00
abstract::The mutagenic activity of the pyrolysis products 2-amino-3-methyl-imidazo[4,5-f]-quinoline 2-amino-3,4-dimethylimidazo[4,5-f]-quinoline in Salmonella typhimurium TA98 using rat intestinal and renal subcellular fractions as activation systems was approximately 1 and 5 revertants per nmol, respectively. This was 1,000 t...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/BF00117825
更新日期:1987-03-01 00:00:00
abstract::Presently, a large effort is being made worldwide to increase the sustainability of industrial development, while preserving not only the quality of the environment but also that of animal and human life. In this work, sea urchin early developmental stages were used as a model to test the effects of the organophosphat...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-008-9061-2
更新日期:2008-12-01 00:00:00
abstract::Gap junctions (GJ) represent a cellular communication system known to influence neuronal differentiation and survival. To assess a putative role of this system for neural effects of tamoxifen (TAM) and raloxifene (RAL), we used the human teratocarcinoma cell line NTera2/D1, retinoic acid (RA)-dependent neuronal differ...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-010-9165-3
更新日期:2010-12-01 00:00:00
abstract::The goal of cancer eradication has been overshadowed despite the continuous improvement in research and generation of novel cancer therapeutic drugs. One of the undeniable existing problems is drug resistance due to which the paradigm of killing all cancer cells is ineffective. Tumor microenvironment plays a crucial r...
journal_title:Cell biology and toxicology
pub_type: 杂志文章,评审
doi:10.1007/s10565-019-09461-z
更新日期:2019-10-01 00:00:00
abstract:BACKGROUND:Heat shock proteins (HSP) are induced during cellular stress. Their role is to chaperone cellular proteins giving protection from denaturation and ultimately preventing cell death. Monocytes are key cells involved in atherosclerosis and are highly responsive to HSP induction. Therefore, we wished to examine ...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-009-9134-x
更新日期:2010-06-01 00:00:00
abstract::Chrysotile is the predominant type of asbestos used in the United States and thus represents the most important source of exposure to asbestos already in place. While the steepest exposure-response observed for lung cancer has been in workers exposed to chrysotile in textile operations, some argue that chrysotile is l...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/BF00121330
更新日期:1991-01-01 00:00:00
abstract::Male albino rats with diabetes induced by the administration of streptozotocin (STZ) (45 mg/kg, i.v.) were treated with oral administration of diphenyl diselenide (DPDS) pre-dissolved in soya bean oil. A significant reduction in blood glucose levels was observed in STZ-induced diabetic rats treated with DPDS compared ...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-008-9095-5
更新日期:2009-08-01 00:00:00
abstract::The kinetic parameters of inhibition of camel retinal acetylcholinesterase (AChE) activity by cycloheximide (CH) were investigated. For the control system, the Michaelis-Menten constant (K(m)) for the hydrolysis of acetylthiocholine iodide was found to be 0.076 mmol/L and the Vmax was 0.547 mumol/min per mg protein. I...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1023/a:1007421124793
更新日期:1998-06-01 00:00:00
abstract::The effect of noncytotoxic doses of argemone oil (AO) and butter yellow (BY), the common adulterants in edible oil, on free radical generation and signaling pathway for cell proliferation in primary cells of gall bladder (GB) was undertaken. AO and BY showed no cytotoxicity at 0.1 μl/ml and 0.1 μg/ml concentration, re...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-011-9207-5
更新日期:2012-06-01 00:00:00
abstract::Interactions between microtubules and filamentous actin (F-actin) are essential to many cellular processes, but their mechanisms are poorly understood. We investigated possible roles of the myosin family of proteins in the interactions between filamentous actin (F-actin) and microtubules of budding yeast Saccharomyces...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1023/a:1013748500662
更新日期:2001-01-01 00:00:00
abstract::Inhibition of endosomal acidification disturbs insulin signaling in both liver and adipose cells. In this study we used MIN6 beta cells to determine whether bafilomycin, a potent inhibitor of the proton-translocating vacuolar ATPase, disrupts insulin signaling in islet beta cells. Pretreatment of MIN6 cells with varyi...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-006-0054-8
更新日期:2006-05-01 00:00:00
abstract::The mesothelial cells (MCs) play an important role in the morpho-functional alterations of the peritoneal membrane (PM) undergoing peritoneal dialysis (PD). MCs, through the epithelial-mesenchymal transition process (EMT), progressively acquire a myofibroblast-like phenotype, promoting peritoneal fibrosis (PF) and fai...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-018-9438-9
更新日期:2019-04-01 00:00:00
abstract::In previous studies cadmium chloride (CdCl2) nonlethally inhibited Y-1 adrenal mouse adrenal tumour cell 20-dihydroxyprogesterone (20DHP) secretion, affecting unstimulated and stimulated steroidogenic pathway sites differently. We studied CdCl2 effects on unstimulated steroidogenesis using Y-1 cells incubated 0.5 h in...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/BF00757184
更新日期:1994-02-01 00:00:00
abstract::We compared the effects of four quaternary benzo[c]phenanthridine alkaloids--chelerythrine, chelilutine, sanguinarine, and sanguilutine--and two quaternary protoberberine alkaloids-berberine and coptisine--on the human cell line HeLa (cervix carcinoma cells) and the yeasts Saccharomyces cerevisiae and Schizosaccharomy...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1023/a:1010907231602
更新日期:2001-01-01 00:00:00