Güney Eskiler, GamzeDeveci Özkan, AsumanHacıefendi, AytenBilir, Cemil2021-10-252021-10-252022Guney Eskiler, G., Deveci Ozkan, A., Haciefendi, A., & Bilir, C. (2021). Mechanisms of abemaciclib, a CDK4/6 inhibitor, induced apoptotic cell death in prostate cancer cells in vitro. Translational oncology, 15(1), 101243. Advance online publication.https://doi.org/10.1016/j.tranon.2021.101243https://hdl.handle.net/20.500.12713/2167The therapeutic effects of abemaciclib (ABE), an inhibitor of cyclin- dependent kinases (CDK) 4/6, on the proliferation of two types of prostate cancer (PC) cells were revealed. In this study, in vitro cytotoxic and apoptotic effects of ABE on metastatic castration-resistant prostate cancer (mCRPC) androgen receptor (AR) negative PC-3 and AR mutant LNCaP PC cells were analyzed with WST-1, Annexin V, cell cycle, reactive oxygen species (ROS), mitochondrial membrane potential, RT-PCR, western blot, and apoptosis protein array. ABE considerably inhibited the growth of PC cells in a dose-dependent manner (p<0.01) and caused significant apoptotic cell death through the suppression of CDK4/6-Cyclin D complex, ROS generation and depolarization of mitochondria membrane potential. However, PC-3 cells were more sensitive to ABE than LNCaP cells. Furthermore, the expression levels of several pro-apoptotic and cell cycle regulatory proteins were upregulated by ABE in especially PC-3 cells with the downregulation of apoptotic inhibitor proteins. Our results suggest that ABE inhibits PC cell growth and promotes apoptosis and thus ABE treatment may be a promising treatment strategy in especially mCRPC. Further preclinical and clinical studies should be performed to clarify the clinical use of ABE for the treatment of PC.eninfo:eu-repo/semantics/openAccessAbemaciclibApoptosisCDK4/6Prostate CancerArticle15134649150WOS:0007299536000042-s2.0-85116878207Q210.1016/j.tranon.2021.101243N/A