title: Binding mode analysis of zerumbone to key signal proteins in the tumor necrosis factor pathway.
abstract: Breast cancer is the second most common cancer among women worldwide. Several signaling pathways have been implicated as causative and progression agents. The tumor necrosis factor (TNF) α protein plays a dual role in promoting and inhibiting cancer depending largely on the pathway initiated by the binding of the protein to its receptor. Zerumbone, an active constituent of Zingiber zerumbet, Smith, is known to act on the tumor necrosis factor pathway upregulating tumour necrosis factor related apoptosis inducing ligand (TRAIL) death receptors and inducing apoptosis in cancer cells. Zerumbone is a sesquiterpene that is able to penetrate into the hydrophobic pockets of proteins to exert its inhibiting activity with several proteins. We found a good binding with the tumor necrosis factor, kinase κB (IKKβ) and the Nuclear factor κB (NF-κB) component proteins along the TNF pathway. Our results suggest that zerumbone can exert its apoptotic activities by inhibiting the cytoplasmic proteins. It inhibits the IKKβ kinase that activates the NF-κB and also binds to the NF-κB complex in the TNF pathway. Blocking both proteins can lead to inhibition of cell proliferating proteins to be downregulated and possibly ultimate induction of apoptosis.
authors: UPM-MAKNA Cancer Research Laboratory, Institute of Biosciences, University Putra Malaysia, 43400 Serdang, Malaysia. ayeshafatima.69@gmail.com.
authors: Ayesha
authors: A
authors: Fatima
authors: UPM-MAKNA Cancer Research Laboratory, Institute of Biosciences, University Putra Malaysia, 43400 Serdang, Malaysia. ahmadbstmm@yahoo.com.
authors: Ahmad Bustamam Hj
authors: AB
authors: Abdul
authors: UPM-MAKNA Cancer Research Laboratory, Institute of Biosciences, University Putra Malaysia, 43400 Serdang, Malaysia. rasedee@gmail.com.
authors: Rasedee
authors: R
authors: Abdullah
authors: Department of Chemistry, Faculty of Science, University Putra Malaysia, 43400 Serdang, Malaysia. rosa.abedi@gmail.com.
authors: Roghayeh Abedi
authors: RA
authors: Karjiban
authors: Department of Chemistry, Faculty of Science, University Malaya, Petaling Jaya, 50603 Selangor, Malaysia. vannajan@gmail.com.
authors: Vannajan Sanghiran
authors: VS
authors: Lee
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D020134:Catalytic Domain; D030562:Databases, Protein; D051550:I-kappa B Kinase / Q000737:chemistry / Q000378:metabolism; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D012717:Sesquiterpenes / Q000737:chemistry / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; C403304:zerumbone; D051550:I-kappa B Kinase
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