TY - JOUR
T1 - Inhibition of histone/lysine acetyltransferase activity kills CoCl2-treated and hypoxia-exposed gastric cancer cells and reduces their invasiveness
AU - Rath, Suvasmita
AU - Das, Lopamudra
AU - Kokate, Shrikant Babanrao
AU - Ghosh, Nilabh
AU - Dixit, Pragyesh
AU - Rout, Niranjan
AU - Singh, Shivaram P.
AU - Chattopadhyay, Subhasis
AU - Ashktorab, Hassan
AU - Smoot, Duane T.
AU - Swamy, Mahadeva M.
AU - Kundu, Tapas K.
AU - Crowe, Sheila E.
AU - Bhattacharyya, Asima
N1 - Funding Information:
This work was supported by Fast Track Grant SR/FT/LS-38/2010 , Science and Engineering Research Board , Govt. of India, to AB; an Indian Council of Medical Research (ICMR) fellowship to SR; fellowships from Department of Atomic Energy (DAE), India, to LD, SBK and PD. The authors thank Mr. Alok Kumar Jena for his assistance in confocal microscopy.
Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
KW - Apoptosis
KW - CTK7A
KW - Cancer metastasis
KW - HAT
KW - Hif1α
KW - Hypoxia
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U2 - 10.1016/j.biocel.2016.11.014
DO - 10.1016/j.biocel.2016.11.014
M3 - Article
C2 - 27890795
AN - SCOPUS:84999143066
SN - 1357-2725
VL - 82
SP - 28
EP - 40
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
ER -