Pharmacological Inhibition of CDK8 in Triple-Negative Breast Cancer Cell Line MDA-MB-468 Increases E2F1 Protein, Induces Phosphorylation of STAT3 and Apoptosis

Abstract

Cyclin-dependent kinase 8 (CDK8) has been identified as a colon cancer oncogene. Since this initial observation, CDK8 has been implicated as a potential driver of other cancers including acute myelogenous leukemia (AML) and some breast cancers. Here, we observed different biological responses to CDK8 inhibition among colon cancer cell lines and the triple-negative breast cancer (TNBC) cell line MDA-MB-468. When treated with CDK8 inhibitor 4, all treated cell lines responded with decreased cell viability and increased apoptosis. In the MDA-MB-468 cell line, the decrease in cell viability was dependent on increased phosphorylation of signal transducer and activator of transcription 3 (STAT3), which is not observed in the colon cancer cell lines. Furthermore, increased STAT3 phosphorylation in 4 treated MDA-MB-468 cells was dependent on increased transcription factor E2F1 protein. These results are consistent with previous reports of exogenous expression of E2F1-induced apoptosis in MDA-MB-468 cells.

Keywords

• CDK8
• E2F1
• STAT3
• MDA-MB-468 cells
• breast cancer
• quinazoline