The Aurora kinase B relocation blocker LXY18 triggers mitotic catastrophe selectively in malignant cells.

ABSTRACT: The mitotic regulator, Aurora kinase B (AURKB), is frequently overexpressed in malignancy and is a target for therapeutic intervention. The compound, LXY18, is a potent, orally available small molecule that inhibits the proper localization of AURKB during late mitosis, without affecting its kinase activity. In this study, we demonstrate that LXY18 elicits apoptosis in cancer cells derived from various indications, but not in non-transformed cell lines. The apoptosis is p53-independent, triggered by a prolonged mitotic arrest and occurs predominantly in mitosis. Some additional cells succumb post-mitotic slippage. We also demonstrate that cancer cell lines refractory to AURKB kinase inhibitors are sensitive to LXY18. The mitotic proteins MKLP2, NEK6, NEK7 and NEK9 are known regulators of AU

SUBMITTER: Kalashova J 

PROVIDER: S-EPMC10615259 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature