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pubmed-article:10210284pubmed:abstractTextMicrocolin A (Mic-1), a marine-derived compound, has been shown to be a novel antiproliferative and immunosuppressive agent. We investigated the ability of Mic-1 and its chemosynthetic analog, microcolin A3 (Mic-3), to induce apoptosis in murine thymocytes. Following incubation of the cells with Mic-1 (10-100 nM) or Mic-3 (10-100 nM), internucleosomal DNA fragmentation in apoptotic cells was detected by agarose gel electrophoresis and the diphenylamine (DPA) assay; the presence of hypodiploid nuclei assessed by propidium iodide (PI) staining; and the percentages of apoptotic and necrotic cells quantified by morphological observation and fluorescein labeled annexin-V binding. Our results show that both Mic-1 and Mic-3 are potent inducers of apoptosis in thymocytes depending on drug concentration and time of exposure, with Mic-3 being more potent than Mic-1 in the induction of apoptosis. Furthermore, flow cytometric analysis using monoclonal antibodies specific to thymocyte subpopulations showed that the proportion of the early immature CD4+ CD8+ T-cell subpopulation in thymocytes was selectively decreased by both agents with a corresponding increase of other subpopulations, indicating that CD4+ CD8+ T cells are the most likely targets of Mic-1 and Mic-3. These in vitro results suggest that the antiproliferative and immunosuppressive properties of both compounds are possibly associated with apoptosis-inducing events and imply that they may have additional potential value as antineoplastic agents.lld:pubmed
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pubmed-article:10210284pubmed:authorpubmed-author:LongleyR ERElld:pubmed
pubmed-article:10210284pubmed:authorpubmed-author:ZhangL HLHlld:pubmed
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pubmed-article:10210284pubmed:dateRevised2006-11-15lld:pubmed
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pubmed-article:10210284pubmed:articleTitleInduction of apoptosis in mouse thymocytes by microcolin A and its synthetic analog.lld:pubmed
pubmed-article:10210284pubmed:affiliationDivision of Biomedical Marine Research, Harbor Branch Oceanographic Institution, Inc., Fort Pierce, FL 34946, USA.lld:pubmed
pubmed-article:10210284pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:10210284pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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