title: Insights into the molecular interactions of thymoquinone with histone deacetylase: evaluation of the therapeutic intervention potential against breast cancer.
abstract: Many HDAC inhibitors have passed through the gateway of clinical trials. However, they have limited therapeutic implications due to their pleiotropic pharmaceutical properties and off-target effects. In view of this, dietary active phytochemicals were evaluated. Based upon the chemical and structural insights of HDAC active pockets, thymoquinone (TQ) was investigated to uncover its active participation in HDAC inhibition. The synergistic analysis of docking and molecular dynamics simulation disclosed the elementary interaction and stability of TQ with human HDACs. The in silico findings were corroborated with an in vitro analysis, demonstrating the efficient role of TQ in the attenuation of global HDAC activity. Furthermore, TQ also elicited downstream effects of HDAC inhibition: reactivation of HDAC target genes (p21 and Maspin), induction of the pro-apoptotic gene Bax, down regulation of the anti-apoptotic gene Bcl-2 and arrest of the cell cycle at the G2/M phase. Finally, the result of a higher cytotoxicity of TQ towards MCF-7 breast cancer cells in comparison to normal cells indicates the potential of TQ to be an anticancer drug.
authors.affiliation: Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha-769008, India. samirp@nitrkl.ac.in skpatra_99@yahoo.com.
authors.forename: Sabnam
authors.initials: S
authors.lastname: Parbin
authors.affiliation: Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha-769008, India. samirp@nitrkl.ac.in skpatra_99@yahoo.com.
authors.forename: Arunima
authors.initials: A
authors.lastname: Shilpi
authors.affiliation: Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha-769008, India. samirp@nitrkl.ac.in skpatra_99@yahoo.com.
authors.forename: Swayamsiddha
authors.initials: S
authors.lastname: Kar
authors.affiliation: Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha-769008, India. samirp@nitrkl.ac.in skpatra_99@yahoo.com.
authors.forename: Nibedita
authors.initials: N
authors.lastname: Pradhan
authors.affiliation: Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha-769008, India. samirp@nitrkl.ac.in skpatra_99@yahoo.com.
authors.forename: Dipta
authors.initials: D
authors.lastname: Sengupta
authors.affiliation: Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha-769008, India. samirp@nitrkl.ac.in skpatra_99@yahoo.com.
authors.forename: Moonmoon
authors.initials: M
authors.lastname: Deb
authors.affiliation: Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha-769008, India. samirp@nitrkl.ac.in skpatra_99@yahoo.com.
authors.forename: Sandip Kumar
authors.initials: SK
authors.lastname: Rath
authors.affiliation: Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha-769008, India. samirp@nitrkl.ac.in skpatra_99@yahoo.com.
authors.forename: Samir Kumar
authors.initials: SK
authors.lastname: Patra
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D016227:Benzoquinones / Q000737:chemistry* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D016415:Sequence Alignment; D013329:Structure-Activity Relationship
chemical_list: D051017:Apoptosis Regulatory Proteins; D016227:Benzoquinones; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; C003466:thymoquinone