Abstract
We discovered a thalidomide analogue [5-hydroxy-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione (5HPP-33)] with antiproliferative activity against nine cancer cell lines in vitro. Flow cytometric analyses showed that the compound caused G2-M arrest, which occurred mainly at the mitotic phase. In addition, immunofluorescence microscopy and in vitro tubulin polymerization studies showed that 5HPP-33 has antimicrotubule activity with a paclitaxel-like mode of action. It is effective against four different paclitaxel-resistant cell lines. Thus, 5HPP-33 represents a potential antitumor agent.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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Antimitotic Agents / chemical synthesis
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Antimitotic Agents / chemistry
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Antimitotic Agents / pharmacology*
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Cell Cycle / drug effects
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Cell Line, Tumor
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Drug Resistance, Neoplasm
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Humans
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Indoles / chemical synthesis
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Indoles / chemistry
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Indoles / pharmacology*
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Isoindoles
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Mice
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Paclitaxel / pharmacology
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Tubulin / drug effects
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Tubulin Modulators / chemical synthesis
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Tubulin Modulators / chemistry
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Tubulin Modulators / pharmacology*
Substances
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2-(2,6-diisopropylphenyl)-5-hydroxy-1H-isoindole-1,3-dione
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Antimitotic Agents
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Antineoplastic Agents
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Indoles
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Isoindoles
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Tubulin
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Tubulin Modulators
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Paclitaxel