Nitric Oxide-Mediated Histone Hyperacetylation in Oral Cancer: Target for a Water-Soluble HAT Inhibitor, CTK7A

被引：101

作者：

Arif, Mohammed ^{[1
]}

Vedamurthy, Bhusainahalli M. ^{[1
]}

Choudhari, Ramesh ^{[1
]}

Ostwal, Yogesh B. ^{[1
]}

Mantelingu, Kempegowda ^{[1
]}

Kodaganur, Gopinath S. ^{[2
]}

Kundu, Tapas K. ^{[1
]}

机构：

[1] JNCASR, Mol Biol & Genet Unit, Transcript & Dis Lab, Bangalore 560064, Karnataka, India

[2] Bangalore Inst Oncol, Bangalore 560027, Karnataka, India

来源：

CHEMISTRY & BIOLOGY | 2010年 / 17卷 / 08期

关键词：

GENE-EXPRESSION; ACETYLTRANSFERASE; CHROMATIN; P300; ACETYLATION; CURCUMIN; PROGRESSION; CBP/P300; PHOSPHORYLATION; NUCLEOPHOSMIN;

D O I：

10.1016/j.chembiol.2010.06.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Altered histone acetylation is associated with several diseases, including cancer. We report here that, unlike in most cancers, histones are found to be highly hyperacetylated in oral squamous cell carcinoma (OSCC; oral cancer) patient samples. Mechanistically, overexpression, as well as enhanced autoacetylation, of p300 induced by nucleophosmin (NPM1) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) causes the hyperacetylation, which is nitric oxide (NO) signal dependent. Inhibition of the histone acetyltransferase (HAT) activity of p300 by a water-soluble, small molecule inhibitor, Hydrazinocurcumin (CTK7A), substantially reduced the xenografted oral tumor growth in mice. These results, therefore, not only establish an epigenetic target for oral cancer, but also implicate a HAT inhibitor (HATi) as a potential therapeutic molecule.

引用

页码：903 / 913

页数：11

共 48 条

[31] The histone acetyltransferase hMOF is frequently downregulated in primary breast carcinoma and medulloblastoma and constitutes a biomarker for clinical outcome in medulloblastoma [J].

Pfister, Stefan ;

Rea, Stephen ;

Taipale, Mikko ;

Mendrzyk, Frank ;

Straub, Beate ;

Ittrich, Carina ;

Thuerigen, Olaf ;

Sinn, Hans Peter ;

Akhtar, Asifa ;

Lichter, Peter .

INTERNATIONAL JOURNAL OF CANCER, 2008, 122 (06) :1207-1213

[32] Inhibition of Lysine Acetyltransferase KAT3B/p300 Activity by a Naturally Occurring Hydroxynaphthoquinone, Plumbagin [J].

Ravindra, Kodihalli C. ;

Selvi, B. Ruthrotha ;

Arif, Mohammed ;

Reddy, B. A. Ashok ;

Thanuja, Gali R. ;

Agrawal, Shipra ;

Pradhan, Suman Kalyan ;

Nagashayana, Natesh ;

Dasgupta, Dipak ;

Kundu, Tapas K. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (36) :24453-24464

[33] Critical loss of CBP/p300 histone acetylase activity by caspase-6 during neurodegeneration [J].

Rouaux, C ;

Jokic, N ;

Mbebi, C ;

Boutillier, S ;

Loeffler, JP ;

Boutillier, AL .

EMBO JOURNAL, 2003, 22 (24) :6537-6549

[34] Histone deacetylase inhibition selectively alters the activity and expression of cell cycle proteins leading to specific chromatin acetylation and antiproliferative effects [J].

Sambucetti, LC ;

Fischer, DD ;

Zabludoff, S ;

Kwon, PO ;

Chamberlin, H ;

Trogani, N ;

Xu, H ;

Cohen, D .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (49) :34940-34947

[35] Global histone modification patterns predict risk of prostate cancer recurrence [J].

Seligson, DB ;

Horvath, S ;

Shi, T ;

Yu, H ;

Tze, S ;

Grunstein, M ;

Kurdistani, SK .

NATURE, 2005, 435 (7046) :1262-1266

[36] Reversible acetylation of chromatin: Implication in regulation of gene expression, disease and therapeutics [J].

Selvi, B. Ruthrotha ;

Kundu, Tapas K. .

Biotechnology Journal, 2009, 4 (03) :375-390

[37] Nitric oxide-induced nuclear GAPDH activates p300/CBP and mediates apoptosis [J].

Sen, Nilkantha ;

Hara, Makoto R. ;

Kornberg, Michael D. ;

Cascio, Matthew B. ;

Bae, Byoung-Il ;

Shahani, Neelam ;

Thomas, Bobby ;

Dawson, Ted M. ;

Dawson, Valina L. ;

Snyder, Solomon H. ;

Sawa, Akira .

NATURE CELL BIOLOGY, 2008, 10 (07) :866-873

[38] Acetylated NPM1 Localizes in the Nucleoplasm and Regulates Transcriptional Activation of Genes Implicated in Oral Cancer Manifestation [J].

Shandilya, Jayasha ;

Swaminathan, Venkatesh ;

Gadad, Shrikanth S. ;

Choudhari, Ramesh ;

Kodaganur, Gopinath S. ;

Kundu, Tapas K. .

MOLECULAR AND CELLULAR BIOLOGY, 2009, 29 (18) :5115-5127

[39] A new curcumin derivative, HBC, interferes with the cell cycle progression of colon cancer cells via antagonization of the Ca2+/calmodulin function [J].

Shim, JS ;

Lee, J ;

Park, HJ ;

Park, SJ ;

Kwon, HJ .

CHEMISTRY & BIOLOGY, 2004, 11 (10) :1455-1463

[40]

Shim JS, 2002, BIOORGAN MED CHEM, V10, P2439

← 1 2 3 4 5 →