Eribulin alone or in combination with the PLK1 inhibitor BI 6727 triggers intrinsic apoptosis in Ewing sarcoma cell lines.

ABSTRACT: In this study, we investigated the molecular mechanisms of eribulin-induced cell death and its therapeutic potential in combination with the PLK1 inhibitor BI 6727 in Ewing sarcoma (ES). Here, we show that eribulin triggers cell death in a dose-dependent manner in a panel of ES cell lines. In addition, eribulin at subtoxic, low nanomolar concentrations acts in concert with BI 6727 to induce cell death and to suppress long-term clonogenic survival. Mechanistic studies reveal that eribulin monotherapy at cytotoxic concentrations and co-treatment with eribulin at subtoxic concentrations together with BI 6727 arrest cells in the M phase of the cell cycle prior to the onset of cell death. This mitotic arrest is followed by increased phosphorylation of BCL-2 and BCL-x_L as well as down

SUBMITTER: WeiΔ LM 

PROVIDER: S-EPMC5581041 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature