Inhibition of histone/lysine acetyltransferase activity kills CoCl 2 -treated and hypoxia-exposed gastric cancer cells and reduces their invasiveness.

Autor: Rath S; 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., Das L; 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., Kokate SB; 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., Ghosh N; 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., Dixit P; 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., Rout N; Oncopathology, Acharya Harihar Regional Cancer Centre, Cuttack, 753007, Odisha, India., Singh SP; Department of Gastroenterology, SCB Medical College, Cuttack, 753007, Odisha, India., Chattopadhyay S; 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., Ashktorab H; Department of Medicine, Howard University, Washington, DC, 20059, USA., Smoot DT; Department of Medicine, Meharry Medical Center, Nashville, TN, 37208, USA., Swamy MM; Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, JNCASR, Jakkur PO, Bangalore 560064, Karnataka, India., Kundu TK; Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, JNCASR, Jakkur PO, Bangalore 560064, Karnataka, India., Crowe SE; School of Medicine, University of California, San Diego, CA, 92093, USA., Bhattacharyya A; 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.
Jazyk: angličtina
Zdroj: The international journal of biochemistry & cell biology [Int J Biochem Cell Biol] 2017 Jan; Vol. 82, pp. 28-40. Date of Electronic Publication: 2016 Nov 23.
DOI: 10.1016/j.biocel.2016.11.014
Abstrakt: 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 (CoCl 2 ), a hypoxia-mimetic chemical, or 1% O 2 . Here, we show that CTK7A-induced hydrogen peroxide (H 2 O 2 ) generation in CoCl 2 -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.
(Copyright © 2016 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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