Targeting cyclin-dependent kinase 6 by vanillin inhibits proliferation of breast and lung cancer cells: Combined computational and biochemical studies.
Cyclin-dependent kinase 6 (CDK6) is a member of serine/threonine kinase family, and its overexpression is associated with cancer development. Thus, it is considered as a potential drug target for anticancer therapies. This study showed the CDK6 inhibitory potential of vanillin using combined experimental and computational methods. Structure-based docking and 200 ns molecular dynamics simulation studies revealed that the binding of vanillin stabilizes the CDK6 structure and provides mechanistic insights into the binding mechanism. Enzyme inhibition and fluorescence-binding studies showed that vanillin inhibits CDK6 with an half maximal inhibitory concentration = 4.99 μM and a binding constant (K) 4.1 × 107 M-1 . Isothermal titration calorimetry measurements further complemented our observations. Studies on human cancer cell lines (MCF-7 and A549) showed that vanillin decreases cell viability and colonization properties. The protein expression studies have further revealed that vanillin reduces the CDK6 expression and induces apoptosis in the cancer cells. In conclusion, our study presents the CDK6-mediated therapeutic implications of vanillin for anticancer therapies.
['Yousuf|Mohd|M|', 'Shamsi|Anas|A|', 'Queen|Aarfa|A|', 'Shahbaaz|Mohd|M|', 'Khan|Parvez|P|', 'Hussain|Afzal|A|', 'Alajmi|Mohamed F|MF|', 'Rizwanul Haque|Qazi M|QM|', 'Imtaiyaz Hassan|Md|M|']
D000072283:A549 Cells D001547:Benzaldehydes D001943:Breast Neoplasms D049109:Cell Proliferation D051361:Cyclin-Dependent Kinase 6 D005260:Female D057809:HEK293 Cells D006801:Humans D008175:Lung Neoplasms D061986:MCF-7 Cells D056004:Molecular Dynamics Simulation D009363:Neoplasm Proteins
cyclin-dependent kinase 6 vanillin anticancer-molecules docking and MD simulations drug design and discovery kinase inhibitor