Abstract:
:Plumbagin (PL) (5-hydroxy-2-methyl-1,4-napthoquinone), a medicinal plant-derived naphthoquinone, was isolated from the roots of the Plumbago zeylanica L. (also known as Chitrak). The roots of P. zeylanica L. have been used in Indian medicine for >2500 years as an anti-atherogenic, cardiotonic, hepatoprotective and neuroprotective agent. We present here that topical application of non-toxic doses (100-500 nmol) of PL to skin elicits dose-dependent inhibition of ultraviolet radiation (UVR)-induced development of squamous cell carcinomas (SCC). In this experiment, FVB/N mice were exposed to UVR (2 kJ/m(2)) three times weekly from a bank of six Kodacel-filtered FS40 sunlamps (∼ 60% UVB and 40% UVA). Carcinoma incidence in mice treated with vehicle, 100, 200 or 500 nmol PL, at 44 weeks post-UVR, were 86, 80 (P = 0.67), 53 (P = 0.12) and 7% (P = 0.0075), respectively. Both vehicle and PL-treated mice gained weight and did not exhibit any signs of toxicity during the entire period of the experiment. Molecular mechanisms associated with inhibition of UVR-induced development of SCC involved induction of apoptosis and inhibition of cell proliferation. Specific findings are that PL treatment (i) inhibited UVR-induced DNA binding of activating protein-1, nuclear factor-kappaB, Stat3 transcription factors and Stat3-regulated molecules (cdc25A and Survivin); (ii) inhibited protein levels of pERK1/2, PI3K85, pAKTSer473, Bcl(2), BclxL, proliferating cell nuclear antigen and cell cycle inhibitory proteins p27 and p21 and (iii) increased UVR-induced Fas-associated death domain expression, poly (ADP-ribose) polymerase protein cleavage and Bax/Bcl(2) ratio. Taken together, our findings suggest that PL may be a novel agent for the prevention of skin cancer.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Sand JM,Bin Hafeez B,Jamal MS,Witkowsky O,Siebers EM,Fischer J,Verma AKdoi
10.1093/carcin/bgr249subject
Has Abstractpub_date
2012-01-01 00:00:00pages
184-90issue
1eissn
0143-3334issn
1460-2180pii
bgr249journal_volume
33pub_type
杂志文章相关文献
CARCINOGENESIS文献大全abstract::Epidemiological studies have suggested that frequent olive oil consumption may be a protective factor against lung cancer formation. Squalene, a characteristic compound in olive oil, is an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and has been proposed to inhibit the farnesylation of ras on...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/19.4.703
更新日期:1998-04-01 00:00:00
abstract::We analyzed a series of young (median age = 52 years) non-smoker lung cancer patients and their unaffected siblings as controls, using a genome-wide 620 901 single-nucleotide polymorphism (SNP) array analysis and a case-control DNA pooling approach. We identified 82 putatively associated SNPs that were retested by ind...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgp315
更新日期:2010-03-01 00:00:00
abstract::Covalent binding of [7-3H]styrene (S) to DNA in vivo was measured and evaluated in a quantitative manner in order to investigate whether DNA adduct formation could form a mechanistic basis for tumor induction in a carcinogenicity bioassay. [7-3H]S was administered by inhalation in a closed chamber to male and female C...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/14.3.355
更新日期:1993-03-01 00:00:00
abstract::The pulmonary adenoma susceptibility 1 (Pas1) gene affects susceptibility to the development of lung adenomas in mice with a subset of the adenomas progressing to adenocarcinoma (ADC). In this study, genotype distributions for 10 polymorphisms in the human counterparts for three mouse candidate Pas1 genes, KRAS, CASC1...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgn048
更新日期:2008-05-01 00:00:00
abstract::An iron chelate, ferric ethylenediamine-N,N'-diacetate [Fe(III)-EDDA], was found to produce hydroxyl radicals with hydrogen peroxide, as determined by both a deoxyribose degradation test and electron spin resonance. Hydroxyl radical production was inhibited not only by adding hydroxyl radical scavengers and catalase, ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/15.12.2817
更新日期:1994-12-01 00:00:00
abstract::p53-upregulated modulator of apoptosis (PUMA) plays an essential role in p53-dependent apoptosis following DNA damage. PUMA also mediates apoptosis independent of p53. In this study, we investigated the role and mechanism of PUMA induction in response to serum starvation in p53-deficient cancer cells. Following serum ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgn150
更新日期:2008-10-01 00:00:00
abstract::To explore the potential role for estrogen in lung cancer susceptibility, candidate single-nucleotide polymorphism (SNPs) in tobacco and estrogen metabolism genes were evaluated. Population-based cases (n = 504) included women aged 18-74, diagnosed with NSCLC in metropolitan Detroit between November 2001 and October 2...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgp033
更新日期:2009-04-01 00:00:00
abstract::Nitric oxide (NO) is a short-lived, pleiotropic molecule that affects numerous critical functions in the body. Presently, there are markedly conflicting findings in the literature regarding NO and its role in carcinogenesis and tumor progression. NO has been shown to have dichotomous effects on cellular proliferation,...
journal_title:Carcinogenesis
pub_type: 杂志文章,评审
doi:10.1093/carcin/bgt034
更新日期:2013-03-01 00:00:00
abstract::Whether single cells immunohistochemically positive for glutathione S-transferase P1-1 (GSTP1-1) induced in the female mouse liver by DEN (Hatayama et al., Carcinogenesis, 14, 537-538, 1993) are precursor initiated cells of preneoplastic foci, is of importance in chemical hepatocarcinogenesis. Nrf2 transactivates a wi...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/23.3.457
更新日期:2002-03-01 00:00:00
abstract::The development of human breast cancer is a complex multi-step process that depends on various exogenous and endogenous factors that modulate the transformation of normal human breast epithelial cells into neoplastic ones. Using a spontaneously-immortalized human breast epithelial (MCF-10F) cell line, we have shown pr...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/22.10.1685
更新日期:2001-10-01 00:00:00
abstract::Cyclooxygenases (COX) catalyse the oxygenation of arachidonic acid to prostaglandin (PG) endoperoxides. Activity of one of the COX isoforms, COX-2, results in production of prostaglandin E(2) (PGE(2)) via the endoperoxide PGH(2). COX-2 has been implicated in the pathogenesis of colorectal cancer. Malondialdehyde (MDA)...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/22.9.1557
更新日期:2001-09-01 00:00:00
abstract::Base excision repair (BER) and nucleotide excision repair (NER) pathways repair damaged DNA, and polymorphisms in these genes might affect breast cancer susceptibility. We evaluated associations between seven single-nucleotide polymorphisms in four DNA repair genes (ERCC4 rs1799801, XPC rs2227998, rs2228001, rs2228000...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgr096
更新日期:2011-08-01 00:00:00
abstract::We have established a protocol that allows qualitative and quantitative determination of butadiene monoepoxide-DNA adducts formed as a result of inhalation exposure to 1,3-butadiene. We observed that in this particular case in vivo samples required extensive sample purification to facilitate a low background. Sample p...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/18.2.439
更新日期:1997-02-01 00:00:00
abstract::To better understand the mechanisms of mutagenesis by the carcinogen, methylene chloride (DCM), we have determined the nature and distribution of forward mutations induced by DCM in the N-terminal region of the lacI gene of Escherichia coli. A total of 116 lacI-d mutations (50 from Uvr+, 66 from UvrB- strain) were cha...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/14.5.789
更新日期:1993-05-01 00:00:00
abstract::Debrisoquine hydroxylase activity has been attributed to CYP2D6 and poor metabolizers of debrisoquine have a reduced relative risk of developing aggressive bladder cancer. Production of a proximate carcinogen could occur in liver or bladder mucosa. However, it is not known if CYP2D6 is expressed in human bladder mucos...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/15.9.1955
更新日期:1994-09-01 00:00:00
abstract::Groups of male and female IF strain mice were fed a diet containing either 0.5% or 1.0% paracetamol for up to 18 months. Among male mice fed the higher dose, the total liver cell tumour incidence was 87%, 21.7% developing hepatocellular carcinomas: both yields were statistically significant. The corresponding incidenc...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/4.4.363-a
更新日期:1983-01-01 00:00:00
abstract::Human papillomavirus (HPV) type 16 infection is an etiologic factor in a subset of head and neck squamous cell carcinomas (HNSCC). It is unknown if host genetic susceptibility modifies the HPV16-HNSCC association. DNA samples collected as part of a Boston area case-control study of HNSCC were genotyped for single-nucl...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgp076
更新日期:2009-06-01 00:00:00
abstract::The inability of cells in culture to grow in medium where methionine is replaced by its metabolic precursor, homocysteine, has been linked to neoplastic transformation and termed 'methionine dependence' or 'methionine auxotrophy'. The present investigation was undertaken to establish the influence of intracellular glu...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.2.241
更新日期:1991-02-01 00:00:00
abstract::Nitric oxide donating aspirin (NO-ASA), consisting of a traditional ASA to which a NO-releasing moiety is covalently attached, is a promising chemopreventive agent against colon cancer. Its mechanism of action is not fully delineated. Here we examined its effect on the expression of the nuclear receptor PPARdelta, who...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgi221
更新日期:2006-02-01 00:00:00
abstract::[14C]Benzo[a]pyrene (BP) was administered to male germfree rats. Urinary metabolites, constituting 9% of the administered radioactivity, were fractionated by lipophilic ion exchange chromatography. More than 80% of the urinary metabolites were conjugated, while neutral metabolites constituted 13-18%. The latter group ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/15.4.681
更新日期:1994-04-01 00:00:00
abstract::Diethylstilbestrol (DES) is a transplacental carcinogen in humans and in rodents. As part of an attempt to examine the mechanism of transplacental carcinogenesis, the transplacental genotoxity of this stilbene estrogen has been investigated. Pregnant hamsters received single injections of 200 mg/kg DES on the 10th day...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.5.773
更新日期:1991-05-01 00:00:00
abstract::Experiments were conducted to determine whether the natural estrogen and an environmental compound with estrogenic action, 4-n-octylphenol (4nOP), could modify tumor development in human c-Ha-ras proto-oncogene transgenic (Tg) rats which are highly susceptible to mammary and skin carcinogens. Female and male Tg and no...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/23.7.1209
更新日期:2002-07-01 00:00:00
abstract::In order to determine the nature of the cytotoxic lesion(s) formed by the antitumour drugs cisplatin and carboplatin, a comparative study was made of bifunctional DNA-adduct formation by these drugs. The kinetics of bifunctional cisplatin adduct formation were studied with DNA in vitro and in cultured Chinese hamster ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/16.10.2447
更新日期:1995-10-01 00:00:00
abstract::Resveratrol (RSVL) is a well-established chemopreventive agent in human breast cancer models. The molecular basis of its action is far less characterized. We investigated the effects of RSVL on activity of adenylate- and guanylate-cyclase (AC, GC) enzymes; two known cytostatic cascades in MCF-7 breast cancer cells. RS...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgg015
更新日期:2003-05-01 00:00:00
abstract::The epidermal growth factor receptor (EGFR) pathway has recently been appreciated as a central mediator of tumorigenesis and an important drug target; however, the influence of genetic variation in this pathway on bladder cancer is not understood. Pathway activation leads to cell proliferation, angiogenesis and is ant...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgp077
更新日期:2009-07-01 00:00:00
abstract::The rates of formation and disappearance of benzo[a]pyrene (B[a]P) DNA-adducts were analyzed in the epidermis of SENCAR mice over a 21-day time course. Mice were treated topically with 200 nmol/mouse of [3H]B[a]P at various times prior to sacrifice. The formation and disappearance of total adducts as well as individua...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/6.5.741
更新日期:1985-05-01 00:00:00
abstract::Maternal nutrition during pregnancy influences the development and metabolism of the fetus. Recent studies suggest that the cancer risk of offspring later in life is associated with maternal diet, but little is known about the effect of a maternal diet high in methyl nutrients on breast cancer risk. Lipotropes are met...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgs125
更新日期:2012-05-01 00:00:00
abstract::Preparations of dietary fibre have an ability to bind potentially toxic compounds in vitro, but it is unclear how the measured binding properties are a reflection of either the relative affinity of such compounds for fibre or the saturation binding capacity of the fibre. Cooking and processing of foods and fermentatio...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/16.2.209
更新日期:1995-02-01 00:00:00
abstract::BTG3/ANA/APRO4 has been reported to be a tumor suppressor gene in some malignancies. It constitutes important negative regulatory mechanism for Src-mediated signaling, a negative regulator of the cell cycle and inhibits transcription factor E2F1. We report that BTG3 is downregulated in renal cancer and that the mechan...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgp042
更新日期:2009-04-01 00:00:00
abstract::A growing body of evidence from human and animal cancer cytogenetics studies indicates that aneuploidy is an important chromosome change in carcinogenesis. To understand the role of this genetic phenomenon during the first steps of an experimental cancer model, molecular and cellular techniques were combined. A sequen...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/16.8.1825
更新日期:1995-08-01 00:00:00