Inhibiting CDK6 activity by quercetin is an attractive strategy for cancer therapy

dc.contributor.authorShahbaaz, Mohd
dc.contributor.authorYousuf, Mohd
dc.contributor.authorKhan, Parvez
dc.date.accessioned2021-01-28T07:14:23Z
dc.date.available2021-01-28T07:14:23Z
dc.date.issued2020
dc.description.abstractCyclin-dependent kinase 6 (CDK6) is a potential drug target that plays an important role in the progression of different types of cancers. We performed in silico and in vitro screening of different natural compounds and found that quercetin has a high binding affinity for the CDK6 and inhibits its activity with an IC50 = 5.89 μM. Molecular docking and a 200 ns whole atom simulation of the CDK6-quercetin complex provide insights into the binding mechanism and stability of the complex. Binding parameters ascertained by fluorescence and isothermal titration calorimetry studies revealed a binding constant in the range of 107 M−1 of quercetin to the CDK6. Thermodynamic parameters associated with the formation of the CDK6−quercetin complex suggested an electrostatic interaction-driven process. The cell-based protein expression studies in the breast (MCF-7) and lung (A549) cancer cells revealed that the treatment of quercetin decreases the expression of CDK6. Quercetin also decreases the viability and colony formation potential of selected cancer cells. Moreover, quercetin induces apoptosis, by decreasing the production of reactive oxygen species and CDK6 expression. Both in silico and in vitro studies highlight the significance of quercetin for the development of anticancer leads in terms of CDK6 inhibitors.en_US
dc.identifier.citationShahbaaz, M. et al. (2020). Inhibiting CDK6 activity by quercetin is an attractive strategy for cancer therapy. ACS Omega ,5(42), 27480-27491en_US
dc.identifier.issn2470-1343
dc.identifier.uri10.1021/acsomega.0c03975
dc.identifier.urihttp://hdl.handle.net/10566/5782
dc.language.isoenen_US
dc.publisherAmerican Chemical Societyen_US
dc.subjectCyclin-dependent kinase 6 (CDK6)en_US
dc.subjectCancer therapyen_US
dc.subjectQuercetinen_US
dc.subjectDrug testingen_US
dc.subjectCDK6 inhibitorsen_US
dc.titleInhibiting CDK6 activity by quercetin is an attractive strategy for cancer therapyen_US
dc.typeArticleen_US

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