Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neocarzinostatin, an antineoplastic agent which consists of a chromophore noncovalently bound to a protein of approximately 10,000D MW, induces the morphological differentiation of cells of the C1300 murine neuroblastoma line in vitro. It also has antimitotic activity, ascribed previously in other cell lines to the action of the chromophore upon DNA. The chromophore is antimitotic for neuroblastoma cells, as well. The morphology-altering effect of neocarzinostatin can also be mimicked by chromophore alone. The morphology-altering effect becomes apparent at doses of the agent which decrease the culture growth rate to approximately 50% of control values. It appears that induction of morphological neural differentiation of neuroblastoma cells requires an increase in the doubling time above a critical value.
 ...
PMID:Neocarzinostatin induces neuronal morphology of mouse neuroblastoma in culture. 252 86

Neocarzinostatin (NCS) is a naturally occurring enediyne antitumor agent that produces single- and double-strand breaks in cellular DNA. We have previously shown that treatment of human (SK-N-SH) and murine (NB41A3) neuroblastoma cells with NCS results in cell death for a subpopulation within the culture. The remaining cells undergo mitotic arrest with morphological differentiation along glial lines. Further investigation of cell death induced by this agent demonstrates that within 24 hr after a single one hr exposure to submicromolar concentrations of NCS, susceptible cells of both lines decrease in size, round up, detach from the culture surface and fragment in the overlying medium. This cytotoxicity is attenuated by the addition of cycloheximide (in NB41A3 cells) or aurintricarboxylic acid (in NB41A3 and SK-N-SH cells). Fluorescence and electron microscopic examination of the nonadherent cells reveals the chromatin condensation and fragmentation characteristic of apoptosis. Examination of the time course of DNA cleavage reveals that despite the presence of alkaline elution-detectable DNA cleavage, oligonucleosomal-sized DNA fragments are not demonstrable by gel electrophoresis immediately after a 1-hr incubation with the drug (1.6-10,000 nM). However, by 6 hr after treatment, DNA ladders are in evidence at all concentrations of NCS. These results suggest that the oligonucleosomal cleavage of DNA seen after NCS treatment is associated with apoptosis, rather than being the direct result of the strand-cleaving effects of the drug itself.
 ...
PMID:Induction of apoptosis in murine and human neuroblastoma cell lines by the enediyne natural product neocarzinostatin. 756 88

Neocarzinostatin is an antineoplastic agent that induces differentiated morphology in human (SK-N-SH) neuroblastoma cells in culture. We have compared this morphological differentiation with that induced by the endogenous differentiation inducer, nerve growth factor (NGF), and have explored the effects of exposure to NGF upon the morphological changes induced by neocarzinostatin in SK-N-SH cells. Both NGF and neocarzinostatin induced process outgrowth in these cells. The processes formed in the presence of NGF however, were shorter and thinner than those induced by neocarzinostatin. Furthermore, only neocarzinostatin induced enlargement of the somata of the cells, and caused cell death in a concentration-dependent fraction of the culture. These distinguishing features of treated cells allowed us to determine whether or not NGF exposure altered responsiveness of the cells to neocarzinostatin. NGF (100-1000 ng/mL) protected SK-N-SH cells from the morphological and cytocidal effects of neocarzinostatin (1-hr exposure, 0.017 to 0.033 micrograms/mL). Protection from neocarzinostatin required that NGF be continuously present for a period beginning 24 hr prior to neocarzinostatin exposure and continuing for the duration of the experiment, implying that the protection afforded by NGF has a latency necessitating pretreatment, and is reversible. These results suggest that neocarzinostatin is taken up by the cells and can exert its effects once NGF is removed, even after neocarzinostatin is washed out of the medium. The signal transduction cascade triggered by NGF receptor binding may prevent the action of neocarzinostatin or the expression of the cellular changes induced in SK-N-SH cells by neocarzinostatin.
 ...
PMID:Prevention of neocarzinostatin-induced cell death and morphologic change in SK-N-SH human neuroblastoma cells by continuous exposure to nerve growth factor. 836 46