Mechanisms of abemaciclib, a CDK4/6 inhibitor, induced apoptotic cell death in prostate cancer cells in vitro

• Published in: Translational oncology Vol. 15; no. 1; p. 101243
• Main Authors: Guney Eskiler, Gamze, Deveci Ozkan, Asuman, Haciefendi, Ayten, Bilir, Cemil
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2022; Neoplasia Press; Elsevier
• Subjects: Abemaciclib; Apoptosis; CDK4/6; Original Research; Prostate cancer; Abemaciclib; CDK4/6; Prostate cancer; Apoptosis
• ISSN: 1936-5233; 1936-5233
• DOI: 10.1016/j.tranon.2021.101243

•ABE treatment may be a promising treatment strategy in especially mCRPC.•ABE treatment significantly inhibited PC cell growth through apoptosis, depolarization of mitochondria membrane potential, the generation of ROS 2. ABE treatment induced depolarization of mitochondria membrane potential.•ABE caused many cytoplasmic vacuoles in PC cells and these effects were more profound in LNCaP cells than PC-3 cells.
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.