TY  - EJOU
AU  - MA, LING 
AU  - JIANG, ZIRUI 
AU  - HOU, XIAO 
AU  - XU, YUTING 
AU  - CHEN, ZIYUN 
AU  - ZHANG, SIYI 
AU  - LI, HANXUE 
AU  - MA, SHAOJIE 
AU  - ZHANG, GENG 
AU  - WANG, XIUJUN 
AU  - JI, NG 

TI  - LA-D-B1, a novel Abemaciclib derivative, exerts anti-breast cancer effects through CDK4/6
T2  - BIOCELL

PY  - 2024
VL  - 48
IS  - 5
SN  - 1667-5746

AB  -  <b>Background:</b> Regulatory proteins involved in human cellular division and proliferation, cyclin-dependent kinases 4 and 6 (CDK4/6) are overexpressed in numerous cancers, including triple-negative breast cancer (TNBC). TNBC is a common pathological subtype of breast cancer that is prone to recurrence and metastasis, and has a single treatment method. As one of the CDK4/6 inhibitors, abemaciclib can effectively inhibit the growth of breast tumors. In this study, we synthesized LA-D-B1, a derivative of Abemaciclib, and investigated its anti-tumor effects in breast cancer. <b>Methods:</b> Cellular viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cloning and migration abilities were determined by colony formation assay and wound healing assay. Cell invasion abilities and adhesion were determined by cell invasion assay and cell adhesion assay. The impact of compound LA-D-B1 on cell proliferation and the cell cycle was analyzed through Western blotting, which quantified the levels of proteins associated with the cyclin-dependent kinase (CDK) 4/6-cyclin D-Rb-E2F pathway. The <i>in vivo</i> anti-tumor activity of compound LA-D-B1 was investigated using a chick chorioallantoic membrane (CAM) model. <b>Results:</b> The study demonstrated that LA-D-B1 effectively suppressed breast cancer cell proliferation, induced apoptosis, and caused cell cycle arrest. Furthermore, LA-D-B1 reduced the expression of key proteins in the CDK4/6-cyclin D-Rb-E2F pathway, including CDK4, CDK6 and E2F1. The results also indicated significant antitumor activity of LA-D-B1 in a transplanted tumor model. <b>Conclusion:</b> In this study, LA-D-B1 demonstrated a potent anti-tumor effect by effectively suppressing cell proliferation and inhibiting cell cycle progression in breast cancer. These findings highlight the potential of LA-D-B1 as a valuable compound for enhancing therapeutic outcomes and controlling the progression of breast cancer.
KW  - CDK4/6 inhibitor; Breast cancer; Antitumor activity; Cell cycle

DO  - 10.32604/biocell.2024.050868