2. Academic Validation
  3. An Aurora kinase inhibitor, AMG900, inhibits glioblastoma cell proliferation by disrupting mitotic progression

An Aurora kinase inhibitor, AMG900, inhibits glioblastoma cell proliferation by disrupting mitotic progression

  • Cancer Med. 2018 Nov;7(11):5589-5603. doi: 10.1002/cam4.1771.
Jaewook Ryu 1,  Jaehyuk Pyo 1,  Chang-Woo Lee 2,  Ja-Eun Kim 1 3
Affiliations

Affiliations

  • 1 Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Korea.
  • 2 Department of Molecular Cell Biology, School of Medicine, Sungkyunkwan University, Suwon, Korea.
  • 3 Department of Pharmacology, School of Medicine, Kyung Hee University, Seoul, Korea.
PMID: 30221846 DOI: 10.1002/cam4.1771
Abstract

The Aurora Kinase family of serine/threonine protein kinases comprises Aurora A, B, and C and plays an important role in mitotic progression. Several inhibitors of Aurora Kinase have been developed as anti-cancer therapeutics. Here, we examined the effects of a pan-Aurora kinase inhibitor, AMG900, against glioblastoma cells. AMG900 inhibited proliferation of A172, U-87MG, and U-118MG glioblastoma cells by upregulating p53 and p21 and subsequently inducing cell cycle arrest and senescence. Abnormal cell cycle progression was triggered by dysregulated Mitosis. Mitosis was prolonged due to a defect in mitotic spindle assembly. Despite the presence of an unattached kinetochore, BubR1, a component of the spindle assembly checkpoint, was not recruited. In addition, Aurora B was not recruited to central spindle at anaphase. Abnormal mitotic progression resulted in accumulation of multinuclei and micronuclei, a type of chromosome missegregation, and ultimately inhibited cell survival. Therefore, the data suggest that AMG900-mediated inhibition of Aurora Kinase is a potential anti-cancer therapy for glioblastoma.

Keywords

AMG900; Aurora kinase; anti-cancer drug; glioblastoma; mitosis.

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