Naringenin as a potential inhibitor of human cyclin-dependent kinase 6: Molecular and structural insights into anti-cancer therapeutics

Cancer is one of the major causes of global deaths and needs immediate therapeutic development. So far, several strategies have been undertaken to prevent cancer, including kinase targeting by small-molecule inhibitors. Cyclin dependent kinase 6 (CDK6) plays an essential role in cancer progression and development as its overexpression is associated with tumor development and progression. The present study demonstrated that Naringenin (NAG) binds strongly to CDK6 with a binding affinity of -7.51 kcal/mol. ATPase assay of CDK6 in the presence of NAG shows that it inhibits CDK6 with an IC50 = 3.13 mu M. Fluorescence and isothermal titration calorimetry studies demonstrated that NAG binds to CDK6 with the binding constant (K) values of 3.55 x 10(6) M-1 and 7.06 +/- 2.70 x 10(6) M-1, respectively. The cell-based functional studies showed that NAG decreases the cell viability of human cancer cell lines, induces apoptosis, and reduces their colonization ability. Outcomes of the present in silico and in vitro studies highlighted the significance of NAG for the development of anti-cancer leads in terms of CDK6 inhibitors and provided future implications for combinatorial anti-cancer therapies.

Automated summary

This study demonstrates that Naringenin (NAG) binds strongly to CDK6 and inhibits its activity. Cell-based experiments show that NAG decreases the cell viability of cancer cells, induces apoptosis, and reduces their colonization ability. These findings highlight the importance of NAG for the development of CDK6 inhibitors and combinatorial anti-cancer therapies.