Abstract
The present data showed that a novel synthesized compound, N-acetyl-N-(4-(4-methoxyphenyl-3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)acetamide (XN05), exhibited potent antitumor activity against various cancer cells in vitro. XN05-treatment in human hepatocellular carcinoma cells resulted in the accumulation of G2/M phase cells and finally induced apoptosis assessed by flow cytometry analysis. Western blot and immunofluorescence experiments indicated that XN05 depolymerized microtubules similar to the effect of combretastatin-A4. In addition, XN05-treatment influenced the expression of cell cycle and apoptosis related proteins in BEL-7402 cells, which was associated with the appearance of phosphorylated Bcl-2. Taken together, all the data demonstrated that XN05 exhibited its antitumor activity through disrupting the microtubule assembly, causing cell cycle arrest and consequently inducing apoptosis in BEL-7402 cells. Therefore, the novel compound XN05 is a promising microtubule inhibitor that has great potentials for therapeutic treatment of various malignancies.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetamides / chemical synthesis
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Acetamides / pharmacology*
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Apoptosis / drug effects
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Carcinoma, Hepatocellular / metabolism
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Carcinoma, Hepatocellular / pathology*
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Caspases / metabolism
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Cell Cycle / drug effects
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Cell Cycle Proteins / metabolism
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Enzyme Activation
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Humans
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Inhibitory Concentration 50
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Isoxazoles / chemical synthesis
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Isoxazoles / pharmacology*
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Liver Neoplasms / metabolism
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Liver Neoplasms / pathology*
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Microtubules / drug effects*
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Microtubules / metabolism
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Microtubules / pathology
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Phosphorylation
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Protein Multimerization
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Stilbenes / pharmacology
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Time Factors
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Tubulin / metabolism*
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Tubulin Modulators / chemical synthesis
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Tubulin Modulators / pharmacology*
Substances
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Acetamides
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Cell Cycle Proteins
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Isoxazoles
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N-acetyl-N-(4-(4-methoxyphenyl-3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)acetamide)
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Proto-Oncogene Proteins c-bcl-2
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Stilbenes
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Tubulin
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Tubulin Modulators
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Caspases
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fosbretabulin