Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.6.1 (sulfatase)
3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

3-O-Methyl-alpha-methyldopamine has been separated by gas-liquid chromatography (GC) as a metabolite of MDA in the urine of dog and monkey. The metabolite was identified as its mono- and di-trifluoroacetyl derivatives by comparison of their GC and GC-mass spectral properties with those of synthetic compounds. The amount of metabolite increased on hydrolyzing the urine from dosed dogs and monkeys with a preparation containing beta-glucuronidase and sulfatase.
...
PMID:Identification of 3-O-methyl-alpha-methyldopamine as a urinary metabolite of 3,4-methylenedioxyamphetamine in dog and monkey. 1 6

Of the total number of breast cancers approx. 30-50% are hormone-dependent and estradiol is one of the main factors of cancerization. Consequently, the control of this hormone inside the cancer cell is of capital importance because it is well established that the inhibition of estradiol biosynthesis can have a positive effect on the evolution of the disease. The blockage of estradiol can be obtained by the action of anti-aromatases, anti-sulfatases, the control of the 17 beta-hydroxysteroid dehydrogenase activity or by the stimulation of the sulfotransferase which converted the estrogens in their sulfates. In breast cancer tissue estrone sulfate is quantitatively the most important source of estradiol. In the intact cell, estrone sulfatase activity is very intense in the hormone-dependent cell lines (e.g. MCF-7, T-47D) but very small activity is observed in the hormone-independent (e.g. MDA-MB-231, MDA-MB-436) cell lines. However, this activity became very strong after homogenization in the hormone-independent cells, suggesting the presence of repressive factor(s) for this enzyme or its sequestering in an inactive form, in the intact cells of these cell lines. In a series of previous studies it was found that in hormone-dependent cell lines different anti-estrogens: tamoxifen and derivatives, ICI 164,384, very significantly decrease the estradiol concentration originated from estrone sulfate, and recently it was observed that Decapeptyl (D-Trp6-gonadotropin-releasing hormone) in the presence of heparin can also decrease the conversion of estrone sulfate into estradiol. No significant effect was obtained in the presence of heparin or Decapeptyl alone. The estrone sulfatase activity can be inhibited by progesterone, the progestagen R-5020, and testosterone. In another series of recent studies the presence of very strong estrogen sulfotransferase activity has been shown in one breast cancer cell line, the MDA-MB-468. We can conclude that: (1) the control of estradiol concentration can be carried out in the breast cancer tissue itself; (2) estrone sulfate can play an important role in the bioavailability of estradiol in the breast cancer cell; and (3) as is the case for the aromatase, the control of: the estrogen sulfatase, estrogen sulfotransferase, and 17 beta-hydroxysteroid dehydrogenase can be new targets for therapeutic applications in breast cancer.
...
PMID:Recent data on estrogen sulfatases and sulfotransferases activities in human breast cancer. 158 Sep 21

Different estrogen-3-sulfates (estrone-3-sulfate, estradiol-3-sulfate, and estriol-3-sulfate) can provoke important biologic responses in different mammary cancer cell lines; there is a significant increase in progesterone receptor. However, no significant effect was observed with estrogen-17-sulfates. The reason for the biologic response of estrogen-3-sulfates is that these sulfates are hydrolyzed, and no sulfatase activity for C17-sulfates is present in these cell lines. [3H]-Estrone sulfate is converted in a very high percentage to estradiol (E2) in different hormone-dependent mammary cancer cell lines (MCF-7, R-27, and T47D), but very little or no conversion was found in hormone-independent mammary cancer cell lines (MDA-MB-231 and MDA-MB-436). Different antiestrogens (tamoxifen and its derivatives) and another potent antiestrogen, ICI 164,384, significantly decrease the concentration of estradiol after incubation of estrone sulfate with the different hormone-dependent mammary cancer cell lines. No significant effect in the uptake and conversion of estrone sulfate was observed in hormone-independent mammary cancer cell lines. The data indicate that sulfatase activity for estrone sulfate is very low in the hormone-independent cell lines; however, comparative kinetic studies carried out after homogenization of MCF-7 and MDA-MB-436 cells show that sulfatase activity is similar, suggesting different mechanisms in the hydrolysis of estrone sulfate in hormone-dependent and hormone-independent cell lines. Progesterone also provokes a significant decrease in uptake and in estradiol levels after incubation of [3H]-estrone sulfate with the MCF-7 cell line. It is concluded that estrogen sulfates can play an important role in the biologic response of estrogens in breast cancer and that control of sulfatase and 17-hydroxysteroid dehydrogenase activities are key steps in the concentration and ability of estradiol in the mammary cancer cell line.
...
PMID:Metabolism and biologic response of estrogen sulfates in hormone-dependent and hormone-independent mammary cancer cell lines. Effect of antiestrogens. 237

Estrogen sulfates are quantitatively the most important form of circulating estrogens during the menstrual cycle and in the post-menopausal period. Huge quantities of estrone sulfate and estradiol sulfate are found in the breast tissues of patients with mammary carcinoma. It has been demonstrated that different estrogen-3-sulfates (estrone-3-sulfate, estradiol-3-sulfate, estriol-3-sulfate) can provoke important biological responses in different mammary cancer cell lines: there is a significant increase in progesterone receptor. On the other hand, no significant effect was observed with estrogen-17-sulfates. The reason for the biological response of estrogen-3-sulfates is that these sulfates are hydrolyzed, and no sulfatase activity for C17-sulfates is present in these cell lines. [3H]Estrone sulfate is converted in a very high percentage to estradiol (E2) in different hormone-dependent mammary cancer cell lines (MCF-7, R-27, T-47D), but very little or no conversion was found in the hormone-independent mammary cancer cell lines (MDA-MB-231, MDA-MB-436). Different anti-estrogens (tamoxifen and derivatives) and another potent anti-estrogen: ICI 164,384, decrease the concentration of estradiol very significantly after incubation of estrone sulfate with the different hormone-dependent mammary cancer cell lines. No significant effect was observed for the uptake and conversion of estrone sulfate in the hormone-independent mammary cancer cell lines. Progesterone provokes an important decrease in the uptake and in estradiol levels after incubation of [3H]estrone sulfate with the MCF-7 cells. It is concluded that in breast cancer: (1) Estrogen sulfates can play an important role in the biological response of estrogens; (2) Anti-estrogens and progesterone significantly decrease the uptake and estradiol levels in hormone-dependent mammary cancer cell lines; (3) The control of the sulfatase and 17 beta-hydroxysteroid dehydrogenase activities, which are key steps in the formation of estradiol in the breast, can open new possibilities in the treatment of hormone-dependent mammary cancer.
...
PMID:Importance of estrogen sulfates in breast cancer. 256 May 11

The metabolism of 17 beta-estradiol in both estrogen receptor positive and negative human breast cancer cell lines has been compared. Initial experiments in which confluent cells were exposed to 1 nM [3H]17 beta-estradiol for 24 h, revealed that the main metabolites formed by estrogen receptor positive MCF-7 and ZR-75-1 cells were 17 beta-estradiol-3-sulfate (together with lesser amounts of estrone sulfate) and estrone. In estrogen receptor negative cell lines, production of estrogen sulfates was either significantly lower (MDA-MB-231 cells) than receptor positive cells, or failed to be produced at all (MDA-MB-330 cells). In both these receptor negative cell lines, production of estrone was significantly higher than in receptor positive cells. Accumulation of estrogen sulfates resulted from attainment of a steady state between synthesis catalysed by estrogen sulfotransferase and degradation catalysed by estrogen sulfatase. The former was present in the cytosol and showed a very high affinity for 17 beta-estradiol and estrone (low nM range). Complex initial velocity versus estrogen substrate curves were obtained with enzyme purified 106-fold by affinity chromatography. Such curves were consistent with a rate equation of degree 3 or 4 and suggest the presence of cooperatively linked dependent binding sites.
...
PMID:Metabolic fate of estradiol in human mammary cancer cells in culture: estrogen sulfate formation and cooperativity exhibited by estrogen sulfotransferase. 320 95

The effects of the polypeptide Decapeptyl (a gonadotropin-releasing hormone (GnRH) agonist analogue) and of transforming growth factor-alpha (TGF-alpha), on estrone sulfate-sulfatase activities in the homogenates of various breast cancer cell lines were studied in the presence of heparin. In hormone-dependent MCF-7 breast cancer cells, Decapeptyl can inhibit sulfatase activity, and this effect is significantly augmented in the presence of heparin. In the other hormone-dependent T-47D breast cancer cell line, the decrease of sulfatase activity was only significant when Decapeptyl was associated with heparin. No significant effect on sulfatase activity elicited by heparin, Decapeptyl or a mixture of both was found in the hormone-independent MDA-MB-231 breast cancer cells. TGF-alpha stimulates sulfatase activity in the MDA-MB-231 cells but has no effect in the MCF-7 cells; in contrast, TGF-alpha combined with heparin provokes a decrease of the sulfatase activity in both cell lines. It is concluded that the sulfatase activity in some types of breast cancer cell can be inhibited by heparin combined with the polypeptides Decapeptyl or TGF-alpha.
...
PMID:Effect of Decapeptyl (a GnRH analogue) and of transforming growth factor-alpha (TGF-alpha), in the presence of heparin, on the sulfatase activity of human breast cancer cells. 774 10

In the present studies the action of Danazol on the conversion of estrone sulfate (E1S) to estradiol (E2) as well as on the sulfatase activity in the MCF-7 and T-47D, hormone-dependent, and MDA-MB-231, hormone-independent, mammary cancer cell lines was explored. Using intact cells we observed that Danazol blocks very significantly the radioactivity uptake and the conversion of [3H]E1S to E2 in all the cells studied. In particular, a very strong effect (85% decrease of these parameters versus the control values) is observed in the T-47D cells. In another series of studies using cell homogenates it is observed that Danazol inhibits the sulfatase activity in all these cell lines. The effect of Danazol is dose-dependent and significant from a concentration of 1 microM. At concentrations of 8 microM E1S, 10(-5) M Danazol, the inhibition of sulfatase activity is 38% in MCF-7, 36% in MDA-MB-231, and 27% in T-47D cells. Analysis by Lineweaver-Burk plot shows that the inhibitory effect is competitive. As E1S is one of the main sources of E2 in human mammary tumors, the present data could open new possibilities for therapeutic applications in hormone-dependent breast cancer.
...
PMID:Action of danazol on the conversion of estrone sulfate to estradiol and on the sulfatase activity in the MCF-7, T-47D and MDA-MB-231 human mammary cancer cells. 833 87

Estrogen levels in breast tumors of post-menopausal women are as much as 10 times higher than in plasma, presumably due to in situ formation of estrogen. Several lines of evidence indicate that the major source of estrogen in breast cancer cells may be from conversion of estrone sulfate to estrone by the enzyme estrone sulfatase. Inhibitors of estrone sulfatase may thus be potential agents for the treatment of estrogen-dependent breast cancer. We designed and synthesized a series of estrone-3-amino derivatives as potential estrone sulfatase inhibitors. We tested the inhibitory potential of these compounds using human placental microsomes, which contain a substantial amount of estrone sulfatase activity. Several compounds in the series significantly inhibited estrone sulfatase activity of the human placental microsomes when present at 10 microM. The IC50 for the estrone-3-amino compounds ranged from 8.7 to 14.6 microM. We next tested the ability of the estrone-3-amino derivatives to inhibit growth of the estrogen-dependent MCF-7 breast cancer cell line. MCF-7 cells showed substantial proliferation in the presence of 100 nM estrone sulfate in estrogen-free media, indicating that the cells were capable of converting estrone sulfate into estrone. The proliferative effect of estrone sulfate (1 microM) was significantly blocked by the estrone-3-amino derivatives at 10 microM. The magnitude of MCF-7 cell inhibition resulting from treatment with the estrone-3 amino compounds was similar to or exceeded that of Danazol, but was less than the level resulting from treatment with estrone sulfamate. Using data from all of the compounds tested, inhibition of MCF-7 cell proliferation was positively correlated with inhibition of placental estrone sulfatase activity, suggesting that the reduction in cell growth was attributable to the blockade of sulfatase activity. In support of this, there was no relationship between inhibition of estrone sulfatase activity and inhibition of cell growth when the estrogen-independent cell line MDA-MB-231 was used. Our results indicate the possible utility of estrone-3-amino derivatives for inhibition of estrone sulfatase activity. Further, our data support the concept that estrone sulfatase inhibitors may be useful as therapeutic agents for estrogen-dependent breast cancers.
...
PMID:Inhibition of placental estrone sulfatase activity and MCF-7 breast cancer cell proliferation by estrone-3-amino derivatives. 900 41

Testing human hair for drugs of abuse is a relatively new technique which requires control before being fully accepted in justice applications. Laboratories must be able to demonstrate that they can accurately determine what drugs are present in unknown hair samples and at what levels. To date few exercises have been organized in USA, Germany and France, all devoted to opiates, cocaine and cannabis. However, the number of drugs which can be detected in hair is growing every day. Among them, amphetamine and related compounds, such as MDMA, are of major interest due to increasing abuse. At the initial state of this work, four different preparation procedures were used to test amphetamine, MDA and MDMA. Direct methanol extraction, acid (HCl 0.1 N), alkaline (NaOH 1 N) and enzymatic (beta-glucuronidase/arylsulfatase) hydrolyses were compared. Best recoveries were observed after alkaline hydrolysis. The same hair sample was powdered and sent to 16 laboratories, in USA (4), Germany (6), France (3), Spain (1), Japan (1) and Korea (1) to test amphetamine, methamphetamine, MDA and MDMA. All laboratories returned results within 3 months. Amphetamine tested positive 13 times with concentrations ranging from 3.3 to 17.5 ng/mg. Only 2 laboratories identified methamphetamine, using GC/MS, at low concentration (0.8 and 1.8 ng/mg), which appears to be a false positive. MDA and MDMA both tested positive in 14 cases, with concentrations ranging from 1.8 to 19.5, and 8.9 to 100.0 ng/mg for MDA and MDMA, respectively. These scattered results clearly indicated that new exercises are needed to ensure quality in hair testing. This is one of the major aims of the Society of Hair Testing.
...
PMID:Interlaboratory comparison of quantitative determination of amphetamine and related compounds in hair samples. 904 20

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.
...
PMID:Development of potent non-estrogenic estrone sulfatase inhibitors. 965 50


1 2 Next >>

---