Skip to Content
Merck
  • 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 medicine (2018-09-18)
Jaewook Ryu, Jaehyuk Pyo, Chang-Woo Lee, Ja-Eun Kim
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-p21WAF1 (Ab-1) Mouse mAb (EA10), liquid, clone EA10, Calbiochem®
Sigma-Aldrich
Anti-phospho-Histone H3 (Ser10) Antibody, Mitosis Marker, Upstate®, from rabbit