Abstract:
:2-Methoxyestradiol (2-ME), an endogenous metabolite of 17beta-estradiol, is present in human blood and urine. Here we show for the first time that 2-ME significantly inhibited the growth of normal prostate epithelial cells and androgen-dependent LNCaP and androgen-independent DU145 prostate cancer cells. This growth inhibition was accompanied by a twofold increase in the G(2)/M population, with a concomitant decrease in the G(1) population, as shown by cell-cycle analysis. 2-ME treatment affected the cell-cycle progression of prostate cancer cells specifically by blocking cells in the G(2) phase. Immunoblot analysis of the key cell-cycle regulatory proteins in the G(2)/M phase showed a 14-fold increase in the expression of p21 and an eightfold increase in the expression of p34 cell division cycle 2 (cdc2). We also found an accumulation of phosphorylated cdc2 after 2-ME treatment. Furthermore, Wee 1 kinase was detectable after 2-ME treatment. 2-ME treatment also led to an increase in the activity of caspase-3, followed by apoptosis, as shown by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate-biotin nick end-labeling and fluorescein isothiocyanate-poly(ADP-ribose) polymerase assay. Estrogen receptor levels did not change after treatment with 2-ME. Examination of the signaling pathways that mediate 2-ME-induced apoptosis showed reduction in the level of p53 expression and its DNA-binding activity. Given the fact that p53 mutations are common in patients with metastatic prostate cancer, our finding that 2-ME-mediated growth inhibition of human prostate cancer cells occurred in a p53-independent manner has considerable clinical significance. These findings, combined with the limited toxicity of 2-ME, may have significant implications for alternative treatment of advanced prostate cancer.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Kumar AP,Garcia GE,Slaga TJdoi
10.1002/mc.1046subject
Has Abstractpub_date
2001-07-01 00:00:00pages
111-24issue
3eissn
0899-1987issn
1098-2744pii
10.1002/mc.1046journal_volume
31pub_type
杂志文章abstract::Human telomerase reverse transcriptase (TERT) gene encodes the catalytic subunit of telomerase and is located on chromosome 5p15, a genomic region which was found to be associated with multiple cancer types. But no associations with colorectal cancer (CRC) have been reported until recently. Therefore, the purpose of t...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21911
更新日期:2012-10-01 00:00:00
abstract::Single nucleotide polymorphisms (SNPs) of matrix metalloproteinase3 (MMP3) promoter in the development and progression of gastric cancer of whole stomach has never been investigated in any population. We conducted a hospital-based case-control study to explore the MMP3 SNPs and their haplotypes with the risk of gastri...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21837
更新日期:2012-10-01 00:00:00
abstract::Obesity increases colorectal cancer (CRC) risk and progression. However, the impact of obesity on CRC in women is dependent on ovarian hormone status. The purpose of this study was to determine the interactive roles of obesity and ovarian hormones on serum markers of inflammation, cell signaling, and transplanted colo...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20720
更新日期:2011-05-01 00:00:00
abstract::Microsatellite instability (MI) and loss of heterozygosity (LOH) were examined in mammary tumors induced in Sprague-Dawley x F344 F1 female rats by 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Examination of 62 microsatellite loci revealed MI in nine of 15 (60%) PhIP-induced mammary tumors, and five of thes...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2744(199603)15:3<176::AID-MC3>3
更新日期:1996-03-01 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest cancers in the world. All-trans retinoic acid (ATRA) is the major physiologically active form of vitamin A, regulating expression of many genes. Disturbances of vitamin A metabolism are prevalent in some cancer cells. The main aim of this work was...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22158
更新日期:2015-09-01 00:00:00
abstract::Paclitaxel is the last choice for the treatment of advanced melanoma as a second-line chemotherapeutic agent, but there are still many cases of intrinsic resistance to paclitaxel in melanoma and the reasons that cause paclitaxel resistance remain unclear. Here, we identified that high expression of SRY-box transcripti...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.23148
更新日期:2020-03-01 00:00:00
abstract::Concern exists regarding peroxisome proliferator (PP) xenobiotic exposure because many PPs are potent hepatocarcinogens in rodents. The mechanism of carcinogenicity induced by PPs is atypical compared with those of other hepatocarcinogens in that the former appears to involve alterations in expression of PP-activated ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199912)26:4<226::aid-mc2>3
更新日期:1999-12-01 00:00:00
abstract::In this report we characterized the transcriptional regulation of the rat mdr1b gene by xenobiotics. The expression of this gene was increased in primary rat hepatocytes and in the H4-II-E hepatoma cell line by exposure to carcinogens such as aflatoxin B1, N-acetoxy-2-acetylaminofluorene, and methyl methanesulfonate. ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940130109
更新日期:1995-05-01 00:00:00
abstract::High levels of the cell growth inhibitor transforming growth factor-beta1 (TGF-beta1) are often found in a variety of human cancers. However, the physiological significance of this overexpression depends on the availability of the biologically active form of TGF-beta1 within the extracellular matrix of the tumor micro...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.10120
更新日期:2003-05-01 00:00:00
abstract:UNLABELLED:Colon carcinogenesis is long known to be associated with ulcerative colitis (UC), a chronic gastrointestinal disorder. Various pre-clinical and clinical studies have shown that melatonin (MEL) has beneficial effects in cancer. However, elucidation of the detailed molecular mechanisms involved in MEL-mediated...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22274
更新日期:2016-03-01 00:00:00
abstract::Obesity and its associated metabolic syndrome (MetS) are recognized risk factors for breast cancer. The molecular basis for this association remains largely unknown. Adipokines, in particular leptin and adiponectin, are thought to form part of the mechanism linking obesity with cancer through their altered expression/...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20764
更新日期:2011-08-01 00:00:00
abstract::Esophageal squamous cell carcinoma (ESCC) is recognized as one of the malignant tumors with poor prognosis. UAP1L1 (UDP-N-acetylglucosamine-1-like-1) affects numerous biological processes, which is a key regulator of the development of malignant tumors. The biological function and molecular mechanism of UAP1L1 in ESCC...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.23278
更新日期:2021-01-12 00:00:00
abstract::Adipose tissue dysregulation, a hallmark of obesity, contributes to a chronic state of low-grade inflammation and is associated with increased risk and progression of several breast cancer subtypes, including claudin-low breast tumors. Unfortunately, mechanistic targets for breaking the links between obesity-associate...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22763
更新日期:2018-03-01 00:00:00
abstract::LEC (Long-Evans with a cinnamon-like coat color) rats develop hepatocellular carcinomas (HCCs) spontaneously. We examined mutations of codons 12, 13, and 61 of the Ha-ras, Ki-ras, and N-ras genes in four HCCs by the polymerase chain reaction (PCR)-single-stranded DNA direct sequencing method. No ras gene mutations wer...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940040405
更新日期:1991-01-01 00:00:00
abstract::Mutations induced by activated benzo[a]pyrene ((+)-anti-B[a]PDE) in Escherichia coli are being investigated, by using both random and adduct-site-specific mutagenesis approaches. A working hypothesis was proposed that the major adduct of (+)-anti-B[a]PDE (formed at N2-Gua) is able to induce different base-substitution...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940130404
更新日期:1995-08-01 00:00:00
abstract::Although many anti-VEGF agents are available for cancer treatment, side effects of these agents limit their application for cancer treatment and prevention. Here we studied the potential use of a diet-based agent as an inhibitor for VEGF production. Using a VEGF reporter assay, our data showed that an extract from cin...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22506
更新日期:2017-02-01 00:00:00
abstract::Recent studies of the individual functionalities of long non-coding RNAs (lncRNAs) in the development and progression of cancer have suggested that HOX transcript antisense RNA (HOTAIR) is capable of reprogramming chromatin organization and promoting cancer cell metastasis. In order to ascertain the expression pattern...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21944
更新日期:2013-11-01 00:00:00
abstract::Xiphophorus fish have been the subject of intensive genetic research for more than 60 yr, primarily because of the availability of a number of interspecific hybrids that are malignant melanoma models with apparently simple oncogene and tumor suppressor gene determinants. The gene map of Xiphophorus is one of the most ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199807)22:3<150::aid-mc2>3
更新日期:1998-07-01 00:00:00
abstract::Liver cirrhosis is a critical state in the natural course of hepatocellular carcinoma (HCC). We sought to investigate the potential of in-depth proteomics to reveal plasma protein signatures that reflect common networks/pathways of liver cirrhosis, and to determine whether the cirrhosis-related signature in plasma is ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21952
更新日期:2014-01-01 00:00:00
abstract::The Ron receptor tyrosine kinase is overexpressed in approximately half of all human colon cancers. Increased Ron expression positively correlates with tumor progression, and reduction of Ron levels in human colon adenocarcinoma cells reverses their tumorigenic properties. Nearly all colon tumors demonstrate loss of t...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20551
更新日期:2009-11-01 00:00:00
abstract::Dietary heterocyclic aromatic amines (HCA) and polyunsaturated fatty acids (PUFA) are both believed to play a role in colon carcinogenesis, and are both substrate for the enzyme cyclooxygenase (COX). In HCA-7 cells, highly expressing isoform COX-2, we investigated the effects of PUFA on prostaglandin synthesis and DNA...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20032
更新日期:2004-07-01 00:00:00
abstract::Rapid advances in multimodality therapy have not significantly improved the overall 5-yr survival of oral cancer patients in the past two decades, thereby underscoring the need for molecular therapeutics. The development of new treatment strategies for more effective management of oral cancer requires identification o...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20048
更新日期:2005-02-01 00:00:00
abstract::The temporal order of replication of several genes was studied in 10T1/2 cells synchronized by release from confluence-induced arrest of proliferation followed by treatment with 2 micrograms/mL aphidicolin for 24 h. DNA subjected to bromodeoxyuridine substitution for 1- or 2-h intervals spanning the S phase was separa...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940010110
更新日期:1988-01-01 00:00:00
abstract::Polyamine metabolism is a highly coordinated process that is essential for normal development and neoplastic growth in mammals. Although polyamine metabolism is a validated pathway for prevention of carcinogenesis, the mechanisms by which polyamines elicit their tumorigenic effects are poorly understood. In this study...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22051
更新日期:2014-02-01 00:00:00
abstract::Many cytotoxic agents kill cells by invoking a specific death pathway termed physiological cell death, or apoptosis. Treatment of a murine hemopoietic stem cell line, FDCP-mix, with methylmethanesulfonate (MMS) or N'-methyl-N'-nitrosourea (MNU) leads to death by apoptosis. Retroviral gene transfer was used to overexpr...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940110109
更新日期:1994-09-01 00:00:00
abstract::Krüppel-like factor 4 (KLF4) is a zinc-finger-containing transcription factor with tumor suppressor activity in various cancer types. Cells that sustain double strand breaks (DSBs) in their DNA due to high levels of reactive oxygen species (ROS) can develop genomic instability, which can result in cancer formation. On...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22161
更新日期:2015-09-01 00:00:00
abstract::Some of the progeny of isolated mouse embryo fibroblasts acquire the ability to grow indefinitely during cultivation, presumably through some mutational events. The relevance of p53 mutations and loss of heterozygosity to the mechanism of such immortal growth capability remains controversial. Since four bases in intro...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940100109
更新日期:1994-05-01 00:00:00
abstract::Polymorphisms in metabolic and DNA repair genes may alter protein function, consequently affecting patients' response to chemo/radiotherapy. We retrospectively assessed whether polymorphisms of glutathione-S-transferase genes GSTM1 (deletion), GSTT1 (deletion), GSTP1 (Ile105Val, rs1695), and DNA repair genes hOGG1 (Se...
journal_title:Molecular carcinogenesis
pub_type: 临床试验,杂志文章
doi:10.1002/mc.21868
更新日期:2012-10-01 00:00:00
abstract::AMP-activated protein kinase (AMPK) is a cellular energy sensor that is conserved in eukaryotes. Although AMPK is traditionally thought to play a major role in the regulation of cellular lipid and protein metabolism, recent discoveries reveal that AMPK inhibits mammalian target of rapamycin (mTOR) signaling and connec...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20793
更新日期:2012-03-01 00:00:00
abstract::Genomic DNA sequences with the ability to assume non-B form secondary structures have been recently shown to be particularly susceptible to genetic instability, an early contributing factor in human disease and cancer development. Transcription appears to play a central role in formation of these structures and in pro...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章,评审
doi:10.1002/mc.20513
更新日期:2009-04-01 00:00:00