Nakiterpiosin targets tubulin and triggers mitotic catastrophe in human cancer cells

Jen Hsuan Wei, Joachim Seemann

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Agents that interfere with mitotic progression by perturbing microtubule dynamics are commonly used for cancer chemotherapy. Here, we identify nakiterpiosin as a novel antimitotic drug that targets microtubules. Nakiterpiosin induces mitotic arrest and triggers mitotic catastrophe in human cancer cells by impairing bipolar spindle assembly. At higher concentration, it alters the interphase microtubule network andsuppresses microtubule dynamics. In the presence of nakiterpiosin, microtubules are no longer arranged in a centrosomal array and centrosome-mediated microtubule regrowth after cold depolymerization is inhibited. However, centrosome organization, the ultrastructure of Golgi stacks, and protein secretion are not affected, suggesting that the drug has minimal toxicity toward other cellular functions. Nakiterpiosin interacts directly with tubulin, inhibits microtubule polymerization in vitro, and decreases polymer mass in cells. Furthermore, it enhances tubulin acetylation and reduces viability of paclitaxel-resistant cancer cells. In conclusion, nakiterpiosin exerts antiproliferative activity by perturbing microtubule dynamics during mitosis that activates the spindle assembly checkpoint and triggers cell death. These findings suggest the potential use of nakiterpiosin as a chemotherapeutic agent.

Original languageEnglish (US)
Pages (from-to)3375-3385
Number of pages11
JournalMolecular Cancer Therapeutics
Volume9
Issue number12
DOIs
StatePublished - Dec 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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