Abstract |
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.
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Authors | Mohd Yousuf, Anas Shamsi, Aarfa Queen, Mohd Shahbaaz, Parvez Khan, Afzal Hussain, Mohamed F Alajmi, Qazi M Rizwanul Haque, Md Imtaiyaz Hassan |
Journal | Journal of cellular biochemistry
(J Cell Biochem)
Vol. 122
Issue 8
Pg. 897-910
(08 2021)
ISSN: 1097-4644 [Electronic] United States |
PMID | 33829554
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2021 Wiley Periodicals LLC. |
Chemical References |
- Benzaldehydes
- Neoplasm Proteins
- vanillin
- CDK6 protein, human
- Cyclin-Dependent Kinase 6
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Topics |
- A549 Cells
- Benzaldehydes
(chemistry, pharmacology)
- Breast Neoplasms
(drug therapy, enzymology)
- Cell Proliferation
(drug effects)
- Cyclin-Dependent Kinase 6
(chemistry, metabolism)
- Female
- HEK293 Cells
- Humans
- Lung Neoplasms
(drug therapy, enzymology)
- MCF-7 Cells
- Molecular Dynamics Simulation
- Neoplasm Proteins
(chemistry, metabolism)
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