Improved ataxia telangiectasia mutated kinase inhibitor KU60019 provides a promising treatment strategy for non-invasive breast cancer

Oncol Lett. 2014 Nov;8(5):2043-2048. doi: 10.3892/ol.2014.2444. Epub 2014 Aug 13.

Abstract

It has previously been reported that KU60019, as a highly effective radiosensitizer, inhibits the DNA damage response and blocks radiation-induced phosphorylation of key ataxia telangiectasia mutated targets in human glioma cells. The present study investigated whether KU60019 affects cell physiological activities and strengthens the efficacy of doxorubicin-induced DNA damage. It was demonstrated that the compound suppressed the proliferation of MCF-7 cells and significantly increased chemosensitization. In addition, KU60019 (without doxorubicin) inhibited MCF-7 cell motility and invasion, potentially by acting on the phosphorylated-Akt and E-cadherin signaling pathways. Although the majority of MCF-7 cells were arrested at the G1/S phase following treatment with KU60019, the combination of the two compounds did not result in such a marked effect on the cell cycle. In conclusion, KU60019 is a potent chemosensitizer in combination with doxorubicin, therefore, it may provide a promising strategy for non-invasive breast cancer.

Keywords: KU60019; ataxia telangiectasia mutated; chemosensitivity; doxorubicin; p-p53 (Ser15).