XN05, a novel synthesized microtubule inhibitor, exhibits potent activity against human carcinoma cells in vitro.

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.

• Authors: Rui Wu, Wanjing Ding, Tao Liu, Hong Zhu, Yongzhou Hu, Bo Yang, Qiaojun He
• Journal: Cancer letters (Cancer Lett) Vol. 285 Issue 1 Pg. 13-22 (Nov 18 2009) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 19647933 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetamides
• Cell Cycle Proteins
• Isoxazoles
• N-acetyl-N-(4-(4-methoxyphenyl-3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)acetamide)
• Proto-Oncogene Proteins c-bcl-2
• Stilbenes
• Tubulin
• Tubulin Modulators
• Caspases
• fosbretabulin

Topics

• Acetamides (chemical synthesis, pharmacology)
• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (metabolism, pathology)
• Caspases (metabolism)
• Cell Cycle (drug effects)
• Cell Cycle Proteins (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Enzyme Activation
• Humans
• Inhibitory Concentration 50
• Isoxazoles (chemical synthesis, pharmacology)
• Liver Neoplasms (metabolism, pathology)
• Microtubules (drug effects, metabolism, pathology)
• Phosphorylation
• Protein Multimerization
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Stilbenes (pharmacology)
• Time Factors
• Tubulin (metabolism)
• Tubulin Modulators (chemical synthesis, pharmacology)