Abstract:
:Histone deacetylase (HDAC) inhibitors have the potential to derepress epigenetically silenced genes in cancer cells, leading to cell cycle arrest and apoptosis. In the present study, we screened several garlic-derived small organosulfur compounds for their ability to inhibit HDAC activity in vitro. Among the organosulfur compounds examined, allyl mercaptan (AM) was the most potent HDAC inhibitor. Molecular modeling, structure activity and enzyme kinetics studies with purified human HDAC8 provided evidence for a competitive mechanism (K(i) = 24 microM AM). In AM-treated human colon cancer cells, HDAC inhibition was accompanied by a rapid and sustained accumulation of acetylated histones in total cellular chromatin. Chromatin immunoprecipitation assays confirmed the presence of hyperacetylated histone H3 on the P21WAF1 gene promoter within 4 h of AM exposure, and there was increased binding of the transcription factor Sp3. At a later time, 24 h after AM treatment, there was enhanced binding of p53 in the distal enhancer region of the P21WAF1 gene promoter. These findings suggest a primary role for Sp3 in driving P21 gene expression after HDAC inhibition by AM, followed by the subsequent recruitment of p53. Induction of p21Waf1 protein expression was detected at time points between 3 and 72 h after AM treatment and coincided with growth arrest in G(1) of the cell cycle. The results are discussed in the context of other anticarcinogenic mechanisms ascribed to garlic organosulfur compounds and the metabolic conversion of such compounds to potential HDAC inhibitors in situ.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Nian H,Delage B,Pinto JT,Dashwood RHdoi
10.1093/carcin/bgn165subject
Has Abstractpub_date
2008-09-01 00:00:00pages
1816-24issue
9eissn
0143-3334issn
1460-2180pii
bgn165journal_volume
29pub_type
杂志文章相关文献
CARCINOGENESIS文献大全abstract::Since the results of an earlier study indicating no effect of dietary fat on dimethylhydrazine (DMH)-induced colon cancer in rats differed from those of other investigators, the present study was initiated to determine if the modulating effect of fat intake on colon tumorigenesis was dependent on the route of DMH admi...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/6.3.349
更新日期:1985-03-01 00:00:00
abstract::Telomerase activity in cancer cells is dependent on the transcriptional regulation of the human telomerase reverse transcriptase (hTERT) gene, encoding the catalytic subunit of human telomerase. We have shown previously that HTLV-1 basic leucine zipper (HBZ), a viral regulatory protein encoded by the human retrovirus,...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgt221
更新日期:2013-11-01 00:00:00
abstract::Proliferation, apoptosis and angiogenesis are critical biologic processes altered during carcinogenesis. Surrogate biomarkers of these processes represent potential intermediate endpoints for short-term intervention studies with preventive and therapeutic agents. We examined the interrelationships among these processe...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/23.10.1701
更新日期:2002-10-01 00:00:00
abstract::Human Papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (HPV+OPSCC) is increasing in prevalence in the United States, as are cases of patients with multiple HPV+OPSCCs (mHPV+OPSCC). mHPV+OPSCCs present a unique opportunity to examine HPV+OPSCC mutation acquisition and evolution. We performed sequenci...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgaa111
更新日期:2020-10-19 00:00:00
abstract::No previous study has examined the association between mitochondrial DNA copy number (mtCN) and skin cancer risk prospectively. We examined the associations between peripheral blood leukocytes mtCN level and the risks of skin cancers in a case-control study nested within the Nurses' Health Study of non-Hispanic White ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgw072
更新日期:2016-09-01 00:00:00
abstract::The O6-alkylguanine-DNA alkyltransferase (ATase) is known to overcome the effects of promutagenic, precarcinogenic O6-alkylguanine induced in DNA by exposure to environmental, chemotherapeutic and dietary alkylating agents. Within an organ, the cell type-specific responses to these agents may be attributed, in part, t...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/14.4.737
更新日期:1993-04-01 00:00:00
abstract::The age-dependence of the induction of pre-neoplastic enzyme-altered hepatic foci was investigated. Rats were exposed (8 h/day, 7 days/week) to 2000 p.p.m. vinyl chloride (VC) either 'transplacentally' (exposure of pregnant females), or immediately after birth for different time intervals (5, 11, 17, 47, 83 days) or f...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/6.1.65
更新日期:1985-01-01 00:00:00
abstract::We have compared liver, kidney and colon DNA damage, as single strand breaks, in mice with different strain-dependent susceptibility to the colon-specific carcinogen 1,2-dimethylhydrazine (DMH). The mouse strains studied were: AKR/J, DBA2 totally resistant; CD1, C57BL/6N moderately susceptible; SWR/J very susceptible ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/9.8.1347
更新日期:1988-08-01 00:00:00
abstract::Sulindac, a widely used non-steroidal anti-inflammatory drug (NSAID), has been shown to inhibit chemically induced carcinogenesis in animal models. In the present study, we have investigated the molecular mechanism by which sulindac affects the activity and expression of the enzymes that mediate the initial detoxifica...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgi359
更新日期:2006-08-01 00:00:00
abstract::Non-classical class Ib (class Ib) genes are found in all jawed vertebrates, including the amphibian Xenopus, which possesses at least 20 distinct Xenopus non-classical class Ib genes (XNCs). As an immune evasion strategy, tumors often downregulate surface expression of classical major histocompatibility complex class ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgu100
更新日期:2014-08-01 00:00:00
abstract::We constructed a complementary DNA (cDNA) library from mRNAs of rat liver induced by an initiating dose of a chemical carcinogen, N-nitrosodiethylamine (DEN). Using a differential hybridization with cDNA probes prepared from mRNAs of control and DEN-treated rat liver, eight cDNAs of which expression was altered by an ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/15.8.1759
更新日期:1994-08-01 00:00:00
abstract::Drug resistance is one of the main obstacles to the successful treatment of cancer. The availability of agents that are highly effective against drug-resistant cancer cells is therefore essential. The present study was performed to examine the anticancer effects of evodiamine, a major constituent of the Chinese herb E...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgi041
更新日期:2005-05-01 00:00:00
abstract::The carcinogenicities of 1-nitropyrene (1-NP), 4-nitropyrene (4-NP), 1,3-dinitropyrene (1,3-DNP), 1,6-dinitropyrene (1,6-DNP), 1,8-dinitropyrene (1,8-DNP), 3-hydroxy-1-nitropyrene (3-OH-1-NP) and a mixture of 6- and 8-hydroxy-1-nitropyrene (6/8-OH-1-NP) were investigated in newborn female rats. Newborn female CD rats ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/16.12.3027
更新日期:1995-12-01 00:00:00
abstract::Azido-PhIP (2-azido-1-methyl-6-phenylimidazo[4,5-b]pyridine) and nitro-PhIP (2-nitro-1-methyl-6-phenylimidazo[4,5-b]pyridine) have been synthesized and characterized chemically. The mutagenic potencies of azido-PhIP (with photoactivation by near UV irradiation), of nitro-PhIP (without exogenous activation) and of the ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.6.1091
更新日期:1991-06-01 00:00:00
abstract::In Thailand, smoking of commercial cigarettes and of handmade cigarettes has drastically increased in recent decades. Cancer of the lung and of the upper aero-digestive tract have also increased in Thailand as they have in many other countries. It is our working hypothesis that the increase of primary cancer of the li...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/20.1.133
更新日期:1999-01-01 00:00:00
abstract::The Bowman-Birk protease inhibitor (BBI) is a legume-derived inhibitor of chymotrypsin and trypsin that has been shown to suppress cellular transformation and tumorigenesis. In the present investigation the effects of various BBI administration schedules were evaluated for suppression of 3-methylcholanthrene (3-MCA)-i...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.5.935
更新日期:1991-05-01 00:00:00
abstract::DNA damage induced by tetrachlorohydroquinone (Cl(4)HQ), the quinonoid metabolite of pentachlorophenol (PCP), was investigated in human HeLa S3 tumor cells. Formation of one major and two minor DNA adducts in cells treated with Cl(4)HQ (50-300 microM) was detected by (32)P-post-labeling assay and the adducts accumulat...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/22.4.635
更新日期:2001-04-01 00:00:00
abstract::Two complementary genetic parameters were followed in liver parenchymal cells during the first steps of rat hepatocarcinogenesis: the expression of nucleolar genes estimated from their silver stainability and the nuclear DNA content determined after Feulgen staining. Putative preneoplastic lesions as foci and nodules ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/8.2.195
更新日期:1987-02-01 00:00:00
abstract::The effect of a deoxycholic acid instillation on colonic epithelium was investigated and compared with the effect of an intervention scheme in which deoxycholic acid (DCA) treated mice received oral supplements of calcium lactate. The morphology of colonic tissue exposed to DCA was markedly affected when compared to t...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/4.9.1205
更新日期:1983-09-01 00:00:00
abstract::Flow cytometric analysis of fibroblasts, normal breast epithelial cells and breast or other cancer cell lines identified variation in the abilities of cell lines to undergo cell cycle arrest as a response to hypoxia. Human mammary epithelial cells (HMEC), normal fibroblasts (Hs68 and WI38), HeLa cervical carcinoma and...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgh274
更新日期:2004-12-01 00:00:00
abstract::Overexpression of ectopic mutant p53 represses wild-type p53-stimulated transcription, known as a dominant negative effect. On the other hand, overexpression of wild-type p53 can repress transcription stimulated by several transcription factors, including hypoxia-inducible factor-1 (HIF-1). Using a panel of well-chara...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/22.6.861
更新日期:2001-06-01 00:00:00
abstract::Apoptosis is a morphologically and biochemically distinct form of cell death which determines specific patterns of tissue size and shape and balances cell proliferation. In the present study, the sequence of cellular proliferative alterations in urinary bladder epithelium associated with uracil-induced reversible urin...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/18.8.1485
更新日期:1997-08-01 00:00:00
abstract::The identification of primary molecular targets of cancer-preventive phytochemicals is essential for a comprehensive understanding of their mechanism of action. In the present study, we investigated the chemopreventive effects and molecular targets of acacetin, a flavonoid found in Robinia p seudoacacia, also known as...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgt266
更新日期:2014-01-01 00:00:00
abstract::The effects of dietary administration of green tea catechins (GTC) were examined using a multi-organ carcinogenesis model. Groups of 15 F344 male rats were initially treated with a single i.p. administration of 100 mg/kg body wt N-diethyl-nitrosamine, 4 i.p. administrations of 20 mg/kg body wt N-methylnitrosourea, 4 s...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/14.8.1549
更新日期:1993-08-01 00:00:00
abstract::Overall rates of tissue protein degradation in vivo during chemical hepatocarcinogenesis were estimated by a double-isotope method as well as from the accumulation of peptide intermediates in protein degradation induced by bestatin. Several parameters estimating rates of cell proliferation and cell loss have been meas...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/14.12.2581
更新日期:1993-12-01 00:00:00
abstract::Overexpression of the helix-loop-helix protein Id-1 has been reported in over 20 types of cancer. While a number of factors have been demonstrated to regulate Id-1 gene transcription, little is known about the mechanisms responsible for its degradation. In this study, we have demonstrated that Id-1 protein stability w...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgi217
更新日期:2006-02-01 00:00:00
abstract::The role of tumor estrogen receptors (ERs) and serum estrogen in lung cancer is inconclusive. We investigated the hypothesis that ERs and functional single-nucleotide polymorphisms in the estrogen biosynthesis pathway are associated with poorer lung cancer survival. Lung cancer patients (n = 305) from a National Cance...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgq156
更新日期:2010-10-01 00:00:00
abstract::Iron exclusion has been used to identify foci of hepatocellular alteration (FHA) in rats exposed to known carcinogens. This study investigates whether basophilic FHA occurring spontaneously in aged female Fischer 344 rats also exclude iron. Female rats 514-544 days of age were given supplemental iron by injection for ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/11.12.2253
更新日期:1990-12-01 00:00:00
abstract::Ovarian cancer is developed from a single layer of thin epithelial cells covering the surface of ovary, named human ovarian surface epithelial cells. Like all primary human cells, human ovarian surface epithelial cells have a finite life span and will go into senescence and eventually die when cultured in vitro. Immor...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgl115
更新日期:2007-01-01 00:00:00
abstract::As we have shown previously [Tardieu,D., Jaeg,J.P., Cadet,J., Embvani,E., Corpet,D.E. and Petit,C. (1998) Cancer Lett, 134, 1-5], a 48-h treatment of 6% dextran sodium sulphate (DSS) in drinking water led to a reproducible 2-fold increase of the mutagenic oxidative lesion 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/21.5.973
更新日期:2000-05-01 00:00:00