Abstract:
:Estrogen levels in breast tumors of post-menopausal women are as much as 10 times higher than estrogen levels in plasma, presumably due to in situ formation of estrogen. The major source of estrogen in breast cancer cells may be conversion of estrone sulfate to estrone by the enzyme estrone sulfatase. Thus, inhibitors of estrone sulfatase have potential for the treatment of estrogen-dependent breast cancers. Several steroidal agents have been developed that are potent estrone sulfatase inhibitors, most notably estrone-3-O-sulfamate. These compounds may have undesired actions, especially estrogenicity. Recently, non-steroidal estrone sulfatase inhibitors have been designed that avoid the problems associated with an active steroid nucleus; however, these have not achieved the potency of estrone-3-O sulfamate. We have designed and synthesized a series of compounds, 17 beta-(N-alkylcarbamoyl)-estra-1,3,5(10)-trien-3-O-sulfamates (6a-d) and 17 beta-(N-alkanoyl)-estra-1,3,5(10)-trien-3-O-sulfamates (11a-d) that combine the structural features of the steroidal estrone sulfatase inhibitors with a membrane insertion region that should increase the affinity for the sulfatase enzyme and decrease the estrogenicity of the steroid. We tested the compounds for estrone sulfatase inhibition by measuring estrone sulfatase activity in intact cultures of human breast cancer cells (MDA-MB-231). We tested for estrogenicity by measuring growth of estrogen-dependent MCF-7 human breast cancer cells. All of the test compounds (10 nM) substantially inhibited estrogen sulfatase activity of intact MDA-MB-231 cells. Dose-response analysis indicated an IC50 of approximately 0.5 nM for two of the compounds (6a and 11a). In the test for estrogenicity, estrone and estrone-3-O-sulfamate significantly stimulated MCF-7 cell growth. In contrast, neither the 17 beta-(N-alkylcarbamoyl)-estra-1,3,5,(10)-trien-3-O-sulfamates++ + nor the 17 beta-(N)-alkanoyl)-estra-1,3,5,(10)-trien-3-O-sulfamates stimulated growth of MCF-7 cells at a concentration of 1 microM, indicating that they are not estrogenic at levels 2000 times greater than their IC50 for estrone sulfatase. Our data indicate the utility of the new compounds for inhibition of breast cancer cell estrone sulfatase activity. Further, our data support the concept that estrone sulfatase inhibitors may be useful as therapeutic agents for estrogen-dependent breast cancers.
journal_name
Steroidsjournal_title
Steroidsauthors
Li PK,Chu GH,Guo JP,Peters A,Selcer KWdoi
10.1016/s0039-128x(98)00044-0subject
Has Abstractpub_date
1998-07-01 00:00:00pages
425-32issue
7-8eissn
0039-128Xissn
1878-5867pii
S0039-128X(98)00044-0journal_volume
63pub_type
杂志文章相关文献
STEROIDS文献大全abstract::Neutral steroids are difficult to analyse using desorption ionisation methods coupled with mass spectrometry (MS). However, steroids with an unhindered ketone group can readily be derivatised with the Girard P (GP) reagent to give GP hydrazones. Steroid GP hydrazones contain a quaternary nitrogen atom and are readily ...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2005.08.002
更新日期:2006-01-01 00:00:00
abstract::Bile acid conjugates are found in human breast cyst fluid in average concentrations about 50-fold greater than those in blood. Because epidemiologic studies have linked colon and breast cancer and aberrant bile acid profiles are associated with colon cancer risk, we decided to study the influence of bile acid conjugat...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(97)00050-0
更新日期:1997-10-01 00:00:00
abstract::To reduce the variability in estradiol (E2) testing and to assure better patient care, standardization of E2 measurements has been recommended. This study aims to assess the accuracy and variability of E2 measurements performed by 11 routine immunological methods and 6 mass spectrometry methods using single donor seru...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2013.12.005
更新日期:2014-04-01 00:00:00
abstract::Two new polyhydroxysteroids isihippurols A (1) and B (2) were isolated from the MeOH extract of the gorgonian Isis hippuris in addition to nine known steroids namely gorgosterol, 3alpha-acetoxy-24-methyl 11beta,18; 18,20beta; 22,25-triepoxy-5alpha-furostane, hippurin-1, 22-epi-hippuristanol, 22-epi-hippurin-1, 3-acety...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(01)00098-8
更新日期:2001-09-01 00:00:00
abstract::Smith-Lemli-Opitz syndrome (SLOS) is caused by deficiency in the terminal step of cholesterol biosynthesis, which is catalyzed by 7-dehydrocholesterol reductase (DHCR7). The disorder exhibits several phenotypic traits including dysmorphia and mental retardation with a broad range of severity. Pathogenesis of SLOS is c...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2007.07.002
更新日期:2007-10-01 00:00:00
abstract::Four new pregnane glycosides, stelmatocryptonoside A, B, C, and D (1-4), were isolated from the stems of Stelmatocrypton khasianum. On the basis of chemical and spectral data, the structures of 1-4 were established as 3beta, 16alpha-dihydroxy-pregn-5-en-20-one-16-O-beta-D-glucopyranosyl-(1-->2)-[beta-D-glucopyranosyl-...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(01)00187-8
更新日期:2002-04-01 00:00:00
abstract::Estradiol-17 beta labeled with deuterium in the positions 2 or 4 can be prepared from 2-chloromercurio-1,3,5(10)-estratriene-3,17 beta-diol 3-methyl ether 17-acetate or 4-chloromercurio-1,3,5(10)-estratriene-3,17 beta-diol, respectively, in refluxing CH3COO(2)H/(2)H2O. The same reaction performed on 4-acetoxymercurio-...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(83)90052-1
更新日期:1983-06-01 00:00:00
abstract::Gene therapy based on gene delivery is a promising strategy for the treatment of various human diseases such as cancer. Cationic lipids represent one of the important synthetic gene delivery systems. There is a great interest in imaging of gene therapy using the biomedical imaging technique positron emission tomograph...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2010.04.009
更新日期:2010-10-01 00:00:00
abstract::Over the past 30 years, numerous studies in invertebrates and vertebrates have established a role of calcium in oocyte maturation as well as in the resumption and progression of follicular development. Polycystic ovarian syndrome (PCO) is characterized by hyperandrogenic chronic anovulation, theca cell hyperplasia, an...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(99)00012-4
更新日期:1999-06-01 00:00:00
abstract::The first natural occurrence of 19-norcholestenone is reported, together with 17 sterols and one other delta 4-3-ketone in the extracts of the Californian gorgonian, Muricea californica (Aurivillius). Six additional demethyl sterols and five additional 4-monomethyl sterols which remain unidentified were also detected....
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(83)90093-4
更新日期:1983-04-01 00:00:00
abstract::7 beta-Methyl-chenodeoxycholic acid (7-MeCDC, 3 alpha, 7 alpha-dihydroxy-7 beta-methyl-5 beta-cholan-24-oic acid), 7 alpha-methyl-ursodeoxycholic acid (7-MeUDC, 3 alpha, 7 beta-dihydroxy-7 alpha-methyl-5 beta-cholan-24-oic acid), 7 xi-methyl-lithocholic acid (7-MeLC, 3 alpha-hydroxy-7 xi-methyl-5 beta-cholan-24-oic ac...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(84)80025-2
更新日期:1984-10-01 00:00:00
abstract::Lung cancer is the most common cause of cancer mortality in male and female patients in the US. The etiology of non-small cell lung cancer (NSCLC) is not fully defined, but new data suggest that estrogens and growth factors promote tumor progression. In this work, we confirm that estrogen receptors (ER), both ERalpha ...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2006.11.019
更新日期:2007-02-01 00:00:00
abstract::This study was designed to describe the time-course changes of catabolic proteins following muscle atrophy induced by 10 days of dexamethasone (DEX). Rats underwent DEX treatment for 1, 3, 5, 7 and 10 days. Body weight (BW) and lean mass were obtained using a dual energy X-ray absorptiometry (DEXA) scan. Muscle ringer...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2015.12.016
更新日期:2016-03-01 00:00:00
abstract::The addition of molybdate to rabbit liver cytosol increased significantly the affinity of the glucocorticoid receptor for [3H] dexamethasone without influencing the concentration of binding sites. This effect was concentration dependent. Analysis of the binding data by curve-fitting and Scatchard plot revealed the occ...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(84)90088-6
更新日期:1984-08-01 00:00:00
abstract::Some properties of immunoreactive estradiol secreted by adrenals and ovaries of immature female rats were studied. It was shown that adrenals and ovaries of 15-day-old animals secrete approximately equal amounts of immunoreactive estradiol, with thin-layer chromatogram of immunoreactive material being identical for bo...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(92)90004-s
更新日期:1992-04-01 00:00:00
abstract::Fast atom bombardment/mass spectrometry or liquid secondary ion mass spectrometry provides the capability for direct analysis of steroid conjugates (sulfates, glucuronides) without prior hydrolysis or derivatization. During the analysis of biologic extracts, limitations on the sensitivity of detection arise from the p...
journal_title:Steroids
pub_type: 杂志文章,评审
doi:10.1016/0039-128x(90)90014-3
更新日期:1990-10-01 00:00:00
abstract::This review lays out the evidence for the role of E2 in homeostatic and hedonic feeding across several species. While significant effort has been expended on homeostatic feeding research, more studies for hedonic feeding need to be conducted (i.e. are there increases in meal size and enhanced motivation to natural foo...
journal_title:Steroids
pub_type: 杂志文章,评审
doi:10.1016/j.steroids.2017.11.011
更新日期:2018-05-01 00:00:00
abstract::Recent reports demonstrate neurotrophic properties of dehydroepiandrosterone sulfate (DHEAS) in men at rest, as well as profound neurotrophic responses to stress in both men and women. Little is known of neuroprotective-neurotrophic effects of DHEAS during stress exposure, either in men or women. This translational st...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2014.05.011
更新日期:2014-09-01 00:00:00
abstract::Six naturally occurring C27 ecdysteroids were isolated and identified from the tobacco hornworm during pupal-adult development five days after peak titer of molting hormone activity. In order of decreasing quantities the hormones were: 20,26-dihydroxyecdysone, 3-epi-20-hydroxyecdysone, 20hydroxyecdysone, 3-epi-20,26-d...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(79)90084-9
更新日期:1979-09-01 00:00:00
abstract::The inhibition of testosterone 5alpha-reductase activity by 3-oxo-4-androstene-17beta-carboxylic acid in the male reproductive organs of the rat was demonstrated in vitro. The medium for incubation of caput epididymis showed the highest concentration of 5alpha-dihydrotestosterone (5alpha-DHT) whereas the highest conce...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(76)90135-5
更新日期:1976-06-01 00:00:00
abstract::A virulent culture of Hymenoscyphus fraxineus, the causal agent of ash dieback, was investigated for its production of secondary metabolites in a 70 L batch fermentation. Chemical analysis of the mycelial extract by means of flash chromatography and preparative HPLC led to the isolation of a new ergostane-type steroid...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2018.03.007
更新日期:2018-07-01 00:00:00
abstract::The crystal structures of chenodeoxycholic acid (CDCA), ursodeoxycholic acid (7beta isomer of CDCA) and their other two epimers (3beta,7alpha- and 3beta,7beta-isomers) have been resolved. The four isomers were recrystallized from p-xylene. CDCA crystal is hexagonal P6(5) while the crystals of the other three isomers a...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2007.03.007
更新日期:2007-06-01 00:00:00
abstract::In demyelinating or non-demyelinating neurodegenerative diseases, increased levels of 7-ketocholesterol (7KC), 7β-hydroxycholesterol (7β-OHC) and 24(S)-hydroxycholesterol (24S-OHC) can be observed in brain lesions. In 158N murine oligodendrocytes, 7KC triggers a complex mode of cell death defined as oxiapoptophagy, in...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2015.02.003
更新日期:2015-07-01 00:00:00
abstract::The sterol mixture isolated from the marine alga Eutreptia viridis consists mainly of delta 5,7-dienes which account for 80% of the free sterols. Eighteen different sterols were detected, including a novel sterol with the rare delta 23-unsaturation, viz. 24-ethylcholesta-5,7,23Z-trien-3 beta-o1. ...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(82)90018-6
更新日期:1982-10-01 00:00:00
abstract::The synthesis of the esters of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) with three bile acids and of the cholesteryl carbonate of norethisterone are described. :This article reports the synthesis of the esters of norethisterone (17 alpha-ethynl-17beta-hydroxyestr-4-en-3-one) with 3 bile acids ...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(83)90103-4
更新日期:1983-03-01 00:00:00
abstract:BACKGROUND:Urinary steroid profiling by GC or GC-MS are established clinical tools to complement other biochemical tests in the diagnosis and investigation of a wide range of adrenocortical disorders, but normative data on adults using the more specific GC-MS are lacking. Our objective was to set up the reference inter...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2008.03.004
更新日期:2008-09-01 00:00:00
abstract::Progesterone, estrone, estradiol-17 beta and corticosterone were quantified simultaneously for the first time in female American kestrel (Falco sparverius) plasma. A mean level for each hormone was determined for the laying and non-laying periods of the summer (April-September), and for February. Means were comparable...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(84)90012-6
更新日期:1984-04-01 00:00:00
abstract::Dehydroepiandrosterone (DHEA) supplementation has been anecdotally considered as a tool to improve body composition and health status. We aimed to verify the impact of DHEA supplementation on traditional measurements of body composition and blood pressure (BP) due to their clinical applicability. A meta-analysis of ra...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2020.108710
更新日期:2020-11-01 00:00:00
abstract::Efforts to develop a novel class of nonsteroidal aromatase inhibitors began with the discovery that the infertility in male rats exposed to high levels of the agricultural fungicide, fenarimol (alpha-(2-chlorophenyl)-alpha-(4-chlorophenyl)-5-pyrimidine-methanol), was attributable to the inhibition of aromatase activit...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(83)90072-7
更新日期:1987-07-01 00:00:00
abstract::Seventeen cholesteryl alkyl ethers were synthesized through alcoholysis of cholesterol p-toluenesulfonate. This method was found superior to the etherification of sodium or potassium cholesterylate with alkyl halides or methanesulfonates, especially for the preparation of long-chain unsaturated aklyl ethers of [7(m)-3...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(80)90109-9
更新日期:1980-01-01 00:00:00