Induction of apoptosis in murine and human neuroblastoma cell lines by the enediyne natural product neocarzinostatin
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 cu...
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Published in | The Journal of pharmacology and experimental therapeutics Vol. 275; no. 1; pp. 479 - 485 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Pharmacology and Experimental Therapeutics
01.10.1995
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0022-3565 1521-0103 |