title: Binding studies and biological evaluation of β-carotene as a potential inhibitor of human calcium/calmodulin-dependent protein kinase IV.
abstract: 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.
authors.affiliation: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India.
authors.forename: Huma
authors.initials: H
authors.lastname: Naz
authors.affiliation: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India.
authors.forename: Parvez
authors.initials: P
authors.lastname: Khan
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, AIIMS, New Delhi, 110029, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Tarique
authors.affiliation: Department of Medical Biotechnology, Yeungnam University, Gyeongsan, 712-749, South Korea.
authors.forename: Safikur
authors.initials: S
authors.lastname: Rahman
authors.affiliation: CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, India.
authors.forename: Abha
authors.initials: A
authors.lastname: Meena
authors.affiliation: Department of Biotechnology, College of Engineering & Technology, IFTM University, Lodhipur-Rajput, Delhi Road, Moradabad, India.
authors.forename: Shahzaib
authors.initials: S
authors.lastname: Ahamad
authors.affiliation: CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, India.
authors.forename: Suaib
authors.initials: S
authors.lastname: Luqman
authors.affiliation: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India.
authors.forename: Asimul
authors.initials: A
authors.lastname: Islam
authors.affiliation: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India.
authors.forename: Faizan
authors.initials: F
authors.lastname: Ahmad
authors.affiliation: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India. Electronic address: mihassan@jmi.ac.in.
authors.forename: Md Imtaiyaz
authors.initials: MI
authors.lastname: Hassan
mesh_terms: D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000378:metabolism* / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D019207:beta Carotene / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; D019207:beta Carotene; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4
keywords: Anticancer activity; Apoptosis; Calcium/calmodulin-dependent protein kinase IV; Kinase inhibitor; β-carotene