AT9283 exhibits antiproliferative effect on tyrosine kinase inhibitor ‑sensitive and ‑resistant chronic myeloid leukemia cells by inhibition of Aurora A and Aurora B.

AT9283 exhibits antiproliferative effect on tyrosine kinase inhibitor‑sensitive and ‑resistant chronic myeloid leukemia cells by inhibition of Aurora A and Aurora B. Oncol Rep. 2020 Nov;44(5):2211-2218 Authors: Takeda T, Tsubaki M, Genno S, Nemoto C, Onishi Y, Yamamoto Y, Imano M, Satou T, Nishida S Abstract Imatinib is the gold standard in the conventional treatment of chronic myeloid leukemia (CML). However, some patients become resistant to imatinib therapy. To overcome this resistance, second‑generation (dasatinib, nilotinib, and bosutinib) and third‑generation (ponatinib) tyrosine kinase inhibitors (TKIs) have been developed and have been shown to be effective against refractory CML. Although these TKIs provide many benefits for patients with CML, advanced patients show resistance even to these TKIs. Therefore, novel therapeutic strategies are urgently needed for the treatment of TKI‑resistant CML patients. AT9283 is a multi‑targeted kinase inhibitor with potent activity against Janus kinase (JAK), Aurora kinases, and Abl. In the present study, we showed that AT9283 significantly decreased the cell viability of both TKI‑sensitive and TKI‑resistant CML cells as determined by trypan blue exclusion assay. In addition, cell cycle analysis, Annexin V assay, and caspase‑3/7 activity assay revealed that AT9283 increased the cell population in the G2/M phase and induced apoptosis. We investigated the molecular mechani...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research