XN05, a novel synthesized microtubule inhibitor, exhibits potent activity against human carcinoma cells in vitro.
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.
Wu
Rui
R
Zhejiang University, Hangzhou, China.
Ding
Wanjing
W
Liu
Tao
T
Zhu
Hong
H
Hu
Yongzhou
Y
Yang
Bo
B
He
Qiaojun
Q
D000081:Acetamides / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006801:Humans; D020128:Inhibitory Concentration 50; D007555:Isoxazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D055503:Protein Multimerization; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000494:pharmacology*
D000081:Acetamides; D018797:Cell Cycle Proteins; D007555:Isoxazoles; C544224:N-acetyl-N-(4-(4-methoxyphenyl-3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)acetamide); D019253:Proto-Oncogene Proteins c-bcl-2; D013267:Stilbenes; D014404:Tubulin; D050257:Tubulin Modulators; D020169:Caspases; C058728:fosbretabulin