Date of Award
Master of Science (M.S.)
Pharmaceutical and Chemical Sciences
Wade A. Russu
Cyclin-dependent kinases (CDKs) and cyclins (Cyclins) are the core molecules in the regulation mechanism of the entire cell cycle. Cell cycle dysregulation is a common feature of human cancers, and inhibitors of cyclin-dependent kinases (CDKs) play a crucial role in cell cycle control and are one of the most promising areas of cancer therapy. We aspired to use our cyclin-dependent kinase 8 (CDK8) inhibitor, Q-12, as a probe for biomarker discovery for CDK8 inhibitor sensitive tumor types. Q-12 shows potent inhibition of cell viability and induction of apoptosis process in some triple-negative breast cancer (TNBC) and colorectal cancer cell lines in vitro. Western blot results indicate that Q-12 decrease p-STAT3 (Ser 727) stabilized p-STAT3 (Tyr 705) cause its upregulation. Cytokines are responsible for the increased phosphorylation of STAT3 (Tyr 705). Q-12 inhibit phosphorylation of CDK8 substrates STAT3 (Ser 727), STAT1 (Ser 727), E2F1 (Ser375) and reduce CDK8 protein levels. Q-12 initially increase E2F1 protein levels activated E2F1 and decrease Mcl-1 protein levels. All results suggest that STAT3 may not play a major role in cell death mechanism while E2F1 may play a major role. The main aim of the study is to investigate CDK8 inhibitor Q-12 effects on CDK8 and CDK8 substrates in triple negative breast cancer cell line MDA-MB-468, in order to better understand the mechanism of anti-proliferative effect of Q-12.
Li, Shengxi. (2022). Investigation of CDK8 inhibitor Q-12 effects on CDK8 and CDK8 substrates in triple negative breast cancer cell line MDA-MB-468. University of the Pacific, Thesis. https://scholarlycommons.pacific.edu/uop_etds/3794
In Copyright. URI: http://rightsstatements.org/vocab/InC/1.0/
This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).