Disease relevance of Neocarzinostatin

• Neocarzinostatin (NCS) is an acidic protein (molecular weight, 10,700) isolated from Streptomyces carzinostaticus that has antitumor activity both in model rodent systems and in humans [1].
• Cellular hypersensitivity to neocarzinostatin in ataxia-telangiectasia skin fibroblasts [2].
• These results indicate that SMANCS should have less systemic toxicity and a better therapeutic effect than NCS [3].
• Subcellular fate of protein antibiotic neocarzinostatin in culture of a lymphoid cell line from Burkitt's lymphoma [4].
• DNA strand breaks induced by Neocarzinostatin in Escherichia coli cells have been characterized [5].

High impact information on Neocarzinostatin

• Two different DNA sequences are protected by bound Int protein against partial digestion by either pancreatic DNAase or neocarzinostatin [6].
• A recently completed study of mutagenesis with neocarzinostatin (NCS) in the lacI gene has prompted us to re-examine some previous studies, of mutagenesis in this gene [7].
• Structures of the protein-chromophore complex and the apoprotein form of neocarzinostatin were determined at 1.8 angstrom resolution [8].
• Targeted enhancement of the biological activity of the antineoplastic agent, neocarzinostatin. Studies in murine neuroblastoma cells [9].
• Facilitated internalization of neocarzinostatin and its lipophilic polymer conjugate, SMANCS, into cytosol in acidic pH [10].

Chemical compound and disease context of Neocarzinostatin

• Consistent with a role for Artemis in repair of terminally blocked double strand breaks in vivo, human cells lacking Artemis exhibited hypersensitivity to x-rays, bleomycin, and neocarzinostatin, which all induce 3'-phosphoglycolate-terminated double strand breaks [11].
• When intracellular cysteine levels were artificially elevated by oxothiazolidine carboxylate treatment of glutathione-depleted cells, neocarzinostatin toxicity was about two-thirds that seen in cells with normal glutathione levels [12].
• A 5'-end-labeled DNA restriction fragment was treated with the nonprotein chromophore of neocarzinostatin under anoxia in the presence of dithiothreitol, conditions known to maximize formation of chromophore-deoxyribose adducts [13].
• Hypersensitivity of the gene to bleomycin or neocarzinostatin, which paralleled deoxyribonuclease I hypersensitivity, was evident only in nuclei isolated from dexamethasone-treated cells [14].
• Although neocarzinostatin (NCS) attacks DNA almost exclusively at adenine and thymine residues in vitro, exposure of Escherichia coli to this antitumor drug resulted in a high frequency of mutations at guanine:cytosine base pairs in the lacI gene [15].

Biological context of Neocarzinostatin

• Nitroaromatic radiation sensitizers substitute for oxygen in neocarzinostatin-induced DNA damage [16].
• Using DNase I and neocarzinostatin "footprinting" techniques, we show that RepC protein specifically binds to a 32-base-pair sequence within the origin that is part of the initiator cistron [17].
• These resistant malignant B cells also escaped DSB-induced apoptosis following exposure to etoposide or neocarzinostatin [18].
• Induction and repair of DNA and chromosome damage by neocarzinostatin in quiescent normal human fibroblasts [19].
• Neocarzinostatin-induced DNA strand scission and subsequent cell cycle traverse in HeLa S3 cells [20].

Anatomical context of Neocarzinostatin

• The effects of environmental pH on the binding and cytotoxicity of the antitumor proteins neocarzinostatin (NCS) and SMANCS [copoly(styrene-maleic acid)-conjugated NCS] to cultured cells were studied by using their fluorescent-labeled derivatives (F-drugs) [10].
• Selective elimination of anti-DNA antibody-producing cells by antiidiotypic antibody conjugated with neocarzinostatin [21].
• The methanol-extractable, nonprotein chromophore of the antitumor, protein antibiotic neocarzinostatin (NCS) has at least the full activity of the parent compound in inhibiting DNA synthesis and growth of HeLa cells and in causing DNA strand breaks in vivo and in vitro [22].
• Inhibition of ligand-independent cap formation of mouse lymphocytes and Raji cells by neocarzinostatin [23].
• We demonstrate herein that induction of Bcl-2 expression in PC12 cells potentiates the induction of apoptosis and differentiation by the enediyne neocarzinostatin [24].

Associations of Neocarzinostatin with other chemical compounds

• We have investigated the sites of DNA damage by the antitumor antibiotics neocarzinostatin and bleomycin by using a 5'-end-labeled DNA fragment of defined sequence as a substrate [25].
• Interestingly, the kedarcidin chromophore appears structurally related to neocarzinostatin yet recognizes specific DNA sequences in a manner similar to calicheamicin gamma 1I, an enediyne with a significantly different structure [26].
• The selective formation of endonuclease-resistant apyrimidinic sites at specific cytosine residues may explain the high frequency of G X C to A X T transitions in the mutational spectrum of neocarzinostatin [27].
• Glutathione dependence of neocarzinostatin cytotoxicity and mutagenicity in Chinese hamster V-79 cells [28].
• Effects of caffeine on neocarzinostatin-induced inhibition of cell cycle traverse in HeLa-S3 cells [29].

Gene context of Neocarzinostatin

• The phosphorylation-dephosphorylation cycle of JNK and p38 by NCS was attenuated in A-T cells [30].
• Addition of the radiomimetic agent neocarzinostatin for 4 h, however, induced a significant increase in IGF-IR levels in cells without ATM function [31].
• Herein, we demonstrate that the chemotherapeutic enediyne antibiotic neocarzinostatin induced Rad51, but not NBS1, nuclear focus formation in a cell- cycle-dependent manner [32].
• RT-PCR analysis revealed that the expressions of fusion-competent myoblast-specific genes lmd, sns, and del were induced in Schneider cells upon treatment with NCS or HU, whereas expressions of three founder cell-specific genes, duf, ants, and rols, were undetectable [33].
• After treatment of HCT116 cells with a radiomimetic compound neocarzinostatin, active Chk2 exists as stable Thr-68-phosphorylated dimers as well as interconvertable Thr-68-unphosphorylated monomers and dimers [34].

Analytical, diagnostic and therapeutic context of Neocarzinostatin

• Radioimmunoassay of neocarzinostatin, an antitumor protein [35].
• Neocarzinostatin sensitivity of A-T cells could therefore serve as a convenient aid for the laboratory diagnosis of A-T [2].
• The effect of the alpha helix-inducing agent, TFE, on all the beta-sheet neocarzinostatin proteins was studied by circular dichroism, fluorescence, and (1)H NMR studies [36].
• In in vivo experiments, xenografts of bcl-2-transfected PC12 cells were more susceptible to NCS toxicity than were xenografts of mock-transfected PC12 cells [37].
• Characterization of the denatured states distribution of neocarzinostatin by small-angle neutron scattering and differential scanning calorimetry [38].

References