The induction of polyploidy or apoptosis by the Aurora A kinase inhibitor MK8745 is p53-dependent

Anticancer activity of the Aurora A kinase inhibitor MK-5108 in non-small-cell lung cancer (NSCLC) in vitro as monotherapy and in combination with chemotherapies

“…Downstream factors of Aurora A may serve as better potential markers of drug sensitivity. The status of the tumor suppressor p53, a substrate of Aurora A, has been reported to affect cell fate in colon cancer cells following treatment with MK-8745 (Nair et al 2012). Aurora A inhibition curtailed cell growth overall, yet induced apoptosis (wild-type p53) or polyploidy (null/mutated p53) depending on cellular p53 status (Nair et al 2012).…”

Depletion of Aurora A leads to upregulation of FoxO1 to induce cell cycle arrest in hepatocellular carcinoma cells

“…It has been reported that Aurora A kinase interacts with p53, and both proteins are functionally associated at multiple levels. 17,[32][33][34] To evaluate the contribution of p53 to the upregulation of FoxO1 in response to Aurora A inhibition, we depleted Aurora A kinase in additional HCC cell lines, including Huh-7 (p53 mutant), Hep3B (p53 deleted) and SK-HEP-1 (p53 wild-type) cells, and determined FoxO1 expression by western blot analysis. While FoxO1 expression was significantly increased in HepG2 and SK-HEP-1 cells by Aurora A knockdown ( Fig.…”

Targeting GD2 ganglioside and aurora A kinase as a dual strategy leading to cell death in cultures of human neuroblastoma cells

“…Phosphorylation of P53 at Ser215 might represent a key mechanism of cell cycle progression, cell survival, and malignant transformation induced by aurora A kinase [21]. On the other hand, aurora A kinase can decrease phosphorylation of P53 at Ser315, and in consequence inhibit P53 [24]. Moreover, aurora A kinase can negatively regulate PHLDA1 protein levels by direct phosphorylation of Ser98 of the protein, leading to its degradation in MDA-MB-231 human breast adenocarcinoma [22].…”