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

[1] Genes of glycolysis are ubiquitously overexpressed in 24 cancer classes [J].

Altenberg, B ;

Greulich, KO .

GENOMICS, 2004, 84 (06) :1014-1020

[2] Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature [J].

Anand, Preetha ;

Thomas, Sherin G. ;

Kunnumakkara, Ajaikumar B. ;

Sundaram, Chitra ;

Harikumar, Kuzhuvelil B. ;

Sung, Bokyung ;

Tharakan, Sheeja T. ;

Misra, Krishna ;

Priyadarsini, Indira K. ;

Rajasekharan, Kallikat N. ;

Aggarwal, Bharat B. .

BIOCHEMICAL PHARMACOLOGY, 2008, 76 (11) :1590-1611

[3] Overexpression of myocyte enhancer factor 2 and histone hyperacetylation in hepatocellular carcinoma [J].

Bai, Xueli ;

Wu, Lihua ;

Liang, TingBo ;

Liu, ZhiQiang ;

Li, JunJian ;

Li, DongLin ;

Xie, HaiYang ;

Yin, ShengYong ;

Yu, Jun ;

Lin, Qi ;

Zheng, ShuSen .

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2008, 134 (01) :83-91

[4] Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription [J].

Balasubramanyam, K ;

Varier, RA ;

Altaf, M ;

Swaminathan, V ;

Siddappa, NB ;

Ranga, U ;

Kundu, TK .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (49) :51163-51171

[5]

Bandyopadhyay D, 2002, CANCER RES, V62, P6231

[6] Covalent modifications of histones during development and disease pathogenesis [J].

Bhaumik, Sukesh R. ;

Smith, Edwin ;

Shilatifard, Ali .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2007, 14 (11) :1008-1016

[7] A mechanism for coordinating chromatin modification and preinitiation complex assembly [J].

Black, Joshua C. ;

Choi, Janet E. ;

Lombardo, Sarah R. ;

Carey, Michael .

MOLECULAR CELL, 2006, 23 (06) :809-818

[8] Anticancer activities of histone deacetylase inhibitors [J].

Bolden, Jessica E. ;

Peart, Melissa J. ;

Johnstone, Ricky W. .

NATURE REVIEWS DRUG DISCOVERY, 2006, 5 (09) :769-784

[9] The diverse functions of histone acetyltransferase complexes [J].

Carrozza, MJ ;

Utley, RT ;

Workman, JL ;

Côté, J .

TRENDS IN GENETICS, 2003, 19 (06) :321-329

[10]

Czesnikiewicz-Guzik M, 2008, J PHYSIOL PHARMACOL, V59, P139

← 1 2 3 4 5 →