Mechanisms of abemaciclib,a CDK4/6 inhibitor,induced apoptotic cell death in prostate cancer cells in vitro |
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| Authors: | Gamze Guney Eskiler Asuman Deveci Ozkan Ayten Haciefendi Cemil Bilir |
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| Affiliation: | aDepartment of Medical Biology, Faculty of Medicine, Sakarya University, Korucuk Campus, Sakarya 54290, Turkey;bDepartment of Medical Biology, Institute of Health Sciences, Sakarya University, Sakarya, Turkey;cDepartment of Medical Oncology, Faculty of Medicine, Istinye University VMMedical Park Pendik Hospital, Istanbul, Turkey |
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| Abstract: | The 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. |
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| Keywords: | Abemaciclib Prostate cancer Apoptosis CDK4/6 |
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