Icaritin inhibits CDK2 expression and activity to interfere with tumor progression

Icaritin has shown antitumor activity in a variety of human solid tumors and myeloid leukemia cells. However, the direct target of icaritin and the underlying mechanisms remain unclear. In our study, CDK2 was found to be a direct target of icaritin in tumor cells. On one hand, icaritin interacted with CDK2 and interfered with CDK2/CyclinE complex formation, resulting in downregulation of CDK2 activity as illustrated with attenuated phosphorylation of FOXO1, Rb, and P27, and E2F/Rb dissociation. On the other hand, icaritin reduced the stability and translation efficiency of CDK2-mRNA by modulating microRNA-597 expression. To be of functional importance, icaritin inhibited proliferation and promoted apoptosis of tumor cells in vitro and in vivo, which was consistent with CDK2 inhibitors-k03861. Our data revealed CDK2 as the direct target of icaritin for its antitumor effects, which may suggest new therapeutics of icaritin or combinational therapeutics involving both icaritin and CDK2 inhibitors for cancers.

 

Comments:

Your study has found that icaritin, a compound with known antitumor activity, directly targets CDK2 in tumor cells. CDK2 is a protein involved in cell cycle regulation and is often dysregulated in cancer. The mechanisms by which icaritin exerts its antitumor effects have been elucidated in your study.

Firstly, icaritin was found to interact with CDK2 and interfere with the formation of the CDK2/CyclinE complex. This disruption resulted in the downregulation of CDK2 activity, as indicated by decreased phosphorylation of FOXO1, Rb, and P27, as well as dissociation of the E2F/Rb complex. These changes are indicative of inhibited cell cycle progression, which is crucial for tumor cell proliferation.

Additionally, icaritin was found to affect the stability and translation efficiency of CDK2-mRNA. It achieved this by modulating the expression of microRNA-597, which in turn influenced CDK2-mRNA levels. By reducing CDK2-mRNA stability and translation efficiency, icaritin further diminished the levels of functional CDK2 protein in tumor cells.

Importantly, the functional significance of targeting CDK2 by icaritin was demonstrated by its effects on tumor cell proliferation and apoptosis. In both in vitro and in vivo experiments, icaritin inhibited tumor cell proliferation and promoted apoptosis, similar to the effects observed with a known CDK2 inhibitor, k03861.

These findings suggest that CDK2 is a direct target of icaritin for its antitumor effects. The study highlights the potential therapeutic implications of icaritin in cancer treatment. It also suggests the possibility of combinational therapies involving icaritin and CDK2 inhibitors for enhanced efficacy against cancers. Further research and clinical studies are warranted to explore the full potential of icaritin and its interactions with CDK2 in cancer therapy.

Related Products

Cat.No.	Product Name	Information
S8100	K03861 (AUZ454)	K03861 (AUZ454) is a type II CDK2 inhibitor with Kd of 50 nM, 18.6 nM, 15.4 nM, and 9.7 nM for CDK2(WT), CDK2(C118L), CDK2(A144C), and CDK2(C118L/A144C), respectlvely.

Related Targets

CDK