title: Inhibition of histone/lysine acetyltransferase activity kills CoCl2-treated and hypoxia-exposed gastric cancer cells and reduces their invasiveness.
abstract: Hypoxia enhances immortality and metastatic properties of solid tumors. Deregulation of histone acetylation has been associated with several metastatic cancers but its effect on hypoxic responses of cancer cells is not known. This study aimed at understanding the effectiveness of the hydrazinocurcumin, CTK7A, an inhibitor of p300 lysine/histone acetyltransferase (KAT/HAT) activity, in inducing apoptosis of gastric cancer cells (GCCs) exposed to cobalt chloride (CoCl2), a hypoxia-mimetic chemical, or 1% O2. Here, we show that CTK7A-induced hydrogen peroxide (H2O2) generation in CoCl2-exposed and invasive gastric cancer cells (GCCs) leads to p38 MAPK-mediated Noxa expression and thereafter, mitochondrial apoptotic events. Noxa induction in normal immortalized gastric epithelial cells after CTK7A and hypoxia-exposure is remarkably less in comparison to similarly-treated GCCs. Moreover, hypoxia-exposed GCCs, which have acquired invasive properties, become apoptotic after CTK7A treatment to a significantly higher extent than normoxic cells. Thus, we show the potential of CTK7A in sensitizing hypoxic and metastatic GCCs to apoptosis induction.
authors.affiliation: School of Biological Sciences, National Institute of Science Education and Research (NISER) Bhubaneswar, HBNI, P.O. Bhimpur-Padanpur, Via Jatni, Dist. Khurda, 752050, Odisha, India.
authors.forename: Suvasmita
authors.initials: S
authors.lastname: Rath
authors.affiliation: School of Biological Sciences, National Institute of Science Education and Research (NISER) Bhubaneswar, HBNI, P.O. Bhimpur-Padanpur, Via Jatni, Dist. Khurda, 752050, Odisha, India.
authors.forename: Lopamudra
authors.initials: L
authors.lastname: Das
authors.affiliation: School of Biological Sciences, National Institute of Science Education and Research (NISER) Bhubaneswar, HBNI, P.O. Bhimpur-Padanpur, Via Jatni, Dist. Khurda, 752050, Odisha, India.
authors.forename: Shrikant Babanrao
authors.initials: SB
authors.lastname: Kokate
authors.affiliation: School of Biological Sciences, National Institute of Science Education and Research (NISER) Bhubaneswar, HBNI, P.O. Bhimpur-Padanpur, Via Jatni, Dist. Khurda, 752050, Odisha, India.
authors.forename: Nilabh
authors.initials: N
authors.lastname: Ghosh
authors.affiliation: School of Biological Sciences, National Institute of Science Education and Research (NISER) Bhubaneswar, HBNI, P.O. Bhimpur-Padanpur, Via Jatni, Dist. Khurda, 752050, Odisha, India.
authors.forename: Pragyesh
authors.initials: P
authors.lastname: Dixit
authors.affiliation: Oncopathology, Acharya Harihar Regional Cancer Centre, Cuttack, 753007, Odisha, India.
authors.forename: Niranjan
authors.initials: N
authors.lastname: Rout
authors.affiliation: Department of Gastroenterology, SCB Medical College, Cuttack, 753007, Odisha, India.
authors.forename: Shivaram P
authors.initials: SP
authors.lastname: Singh
authors.affiliation: School of Biological Sciences, National Institute of Science Education and Research (NISER) Bhubaneswar, HBNI, P.O. Bhimpur-Padanpur, Via Jatni, Dist. Khurda, 752050, Odisha, India.
authors.forename: Subhasis
authors.initials: S
authors.lastname: Chattopadhyay
authors.affiliation: Department of Medicine, Howard University, Washington, DC, 20059, USA.
authors.forename: Hassan
authors.initials: H
authors.lastname: Ashktorab
authors.affiliation: Department of Medicine, Meharry Medical Center, Nashville, TN, 37208, USA.
authors.forename: Duane T
authors.initials: DT
authors.lastname: Smoot
authors.affiliation: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, JNCASR, Jakkur PO, Bangalore 560064, Karnataka, India.
authors.forename: Mahadeva M
authors.initials: MM
authors.lastname: Swamy
authors.affiliation: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, JNCASR, Jakkur PO, Bangalore 560064, Karnataka, India.
authors.forename: Tapas K
authors.initials: TK
authors.lastname: Kundu
authors.affiliation: School of Medicine, University of California, San Diego, CA, 92093, USA.
authors.forename: Sheila E
authors.initials: SE
authors.lastname: Crowe
authors.affiliation: School of Biological Sciences, National Institute of Science Education and Research (NISER) Bhubaneswar, HBNI, P.O. Bhimpur-Padanpur, Via Jatni, Dist. Khurda, 752050, Odisha, India. Electronic address: asima@niser.ac.in.
authors.forename: Asima
authors.initials: A
authors.lastname: Bhattacharyya
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D003035:Cobalt / Q000494:pharmacology; D003474:Curcumin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D050881:E1A-Associated p300 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006834:Hydrazines / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism; D012995:Solubility; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000072258:Tumor Hypoxia / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D006834:Hydrazines; D017382:Reactive Oxygen Species; C475807:hydrazinocurcumin; D003035:Cobalt; D006861:Hydrogen Peroxide; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; C018021:cobaltous chloride; D003474:Curcumin
keywords: Apoptosis; CTK7A; Cancer metastasis; HAT; Hif1α; Hypoxia