Binding studies and biological evaluation of β-carotene as a potential inhibitor of human calcium/calmodulin-dependent protein kinase IV

Int J Biol Macromol. 2017 Mar;96:161-170. doi: 10.1016/j.ijbiomac.2016.12.024. Epub 2016 Dec 9.


Human calcium/calmodulin-dependent protein kinase IV (CAMKIV), a member of Ser/Thr kinase family, is associated with cancer, cerebral hypoxia and neurodegenerative diseases. β-carotene is a colored organic compound, abundant in plants and fruits and is used in cancer prevention. Here, we report a strong binding affinity of β-carotene with CAMKIV using molecular docking, fluorescence binding and isothermal titration calorimetry methods. Furthermore, β-carotene also reduces the enzyme activity of CAMKIV moderately as observed during ATPase assay. To see the role of β-carotene on cell proliferation and apoptosis, cancerous cells (HeLa, HuH7and MCF-7) and normal (HEK-293-T) cell lines were used. Admirable anticancer activity of β-carotene was observed. We further performed propidium iodide and DAPI (4',6-diamidino-2-phenylindole) assays to understand the mechanism of anticancer activity of β-carotene at molecular level. Our findings provide a newer insight into the use of β-carotene in cancer prevention and protection via inhibition of CAMKIV by regulating the signaling pathways.

Keywords: Anticancer activity; Apoptosis; Calcium/calmodulin-dependent protein kinase IV; Kinase inhibitor; β-carotene.

MeSH terms

  • Calcium-Calmodulin-Dependent Protein Kinase Type 4 / antagonists & inhibitors*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 4 / chemistry
  • Calcium-Calmodulin-Dependent Protein Kinase Type 4 / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Molecular Docking Simulation
  • Protein Conformation
  • Protein Kinase Inhibitors / metabolism*
  • Protein Kinase Inhibitors / pharmacology*
  • Signal Transduction / drug effects
  • beta Carotene / metabolism*
  • beta Carotene / pharmacology*


  • Protein Kinase Inhibitors
  • beta Carotene
  • Calcium-Calmodulin-Dependent Protein Kinase Type 4