Pharicin A, a novel natural ent-kaurene diterpenoid, induces mitotic arrest and mitotic catastrophe of cancer cells by interfering with BubR1 function.

In this study, we report the functional characterization of a new ent-kaurene diterpenoid termed pharicin A, which was originally isolated from Isodon, a perennial shrub frequently used in Chinese folk medicine for tumor treatment. Pharicin A induces mitotic arrest in leukemia and solid tumor-derived cells identified by their morphology, DNA content and mitotic marker analyses. Pharicin A-induced mitotic arrest is associated with unaligned chromosomes, aberrant BubR1 localization and deregulated spindle checkpoint activation. Pharicin A directly binds to BubR1 in vitro, which is correlated with premature sister chromatid separation in vivo. Pharicin A also induces mitotic arrest in paclitaxel-resistant Jurkat and U2OS cells. Combined, our study strongly suggests that pharicin A represents a novel class of small molecule compounds capable of perturbing mitotic progression and initiating mitotic catastrophe, which merits further preclinical and clinical investigations for cancer drug development.
AuthorsHan-Zhang Xu, Ying Huang, Ying-Li Wu, Yong Zhao, Wei-Lie Xiao, Qi-Shan Lin, Han-Dong Sun, Wei Dai, Guo-Qiang Chen
JournalCell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 9 Issue 14 Pg. 2897-907 (Jul 15 2010) ISSN: 1551-4005 [Electronic] United States
PMID20603598 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Diterpenes, Kaurane
  • pharicin A
  • BUB1 protein, human
  • Bub1 spindle checkpoint protein
  • Protein-Serine-Threonine Kinases
  • CDC2 Protein Kinase
  • Antineoplastic Agents (chemistry, isolation & purification, pharmacology)
  • CDC2 Protein Kinase (metabolism)
  • Chromatids (drug effects)
  • Diterpenes, Kaurane (chemistry, isolation & purification, pharmacology)
  • Humans
  • Isodon (chemistry)
  • Jurkat Cells
  • Medicine, Chinese Traditional
  • Mitosis (drug effects)
  • Protein-Serine-Threonine Kinases (analysis, antagonists & inhibitors, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: