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

Human calcium/calmodulin-dependent protein kinase IV (CAMKIV), a member of Ser/Thr kinase family, is associated with cancer, cerebral hypoxia and neurodegenerative diseases. beta-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 beta-carotene with CAMKIV using molecular docking, fluorescence binding and isothermal titration calorimetry methods. Furthermore, beta-carotene also reduces the enzyme activity of CAMKIV moderately as observed during ATPase assay. To see the role of beta-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 beta-carotene was observed. We further performed propidium iodide and DAPI (4',6-diamidino-2-phenylindole) assays to understand the mechanism of anticancer activity of beta-carotene at molecular level. Our findings provide a newer insight into the use of beta-carotene in cancer prevention and protection via inhibition of CAMKIV by regulating the signaling pathways. (C) 2016 Elsevier B.V. All rights reserved.