Daidzein Sulfoconjugates Are Potent Inhibitors of Sterol Sulfatase (EC 3.1.6.2)

Wong, Chun‐Kwok; Keung, Wing Ming

doi:10.1006/bbrc.1997.6502

Cited by 80 publications

(39 citation statements)

References 25 publications

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“…Enzymatic characterization of SULT2B1b indicated that this isozyme is selective for the sulfation of 3b-hydroxysteroids such as cholesterol and hydroxycholesterols and shows little reactivity with 3a-hydroxysteroids of the 3-phenolic hydroxyl group of estrogens (33). This selective reactivity for the 3b-hydroxyl configuration of hydroxysteroids is in contrast to the broader reactivity of SULT2As, which conjugate both 3a-and 3b-hydroxysteroids as well as estrogens (34,35).…”

Section: Discussionmentioning

confidence: 99%

Biosynthesis of the regulatory oxysterol, 5-cholesten-3β,25-diol 3-sulfate, in hepatocytes

Pandak

Erickson

et al. 2007

Journal of Lipid Research

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Cellular cholesterol homeostasis is maintained through coordinated regulation of cholesterol synthesis, degradation, and secretion. Nuclear receptors for oxygenated cholesterol derivatives (oxysterols) are known to play key roles in the regulation of cholesterol homeostasis. We recently identified a sulfated oxysterol, 5-cholesten-3b,25-diol 3-sulfate (25HC3S), that is localized to liver nuclei. The present study reports a biosynthetic pathway for 25HC3S in hepatocytes. Assays using mitochondria isolated from rats and sterol 27-hydroxylase (Cyp27A1) gene knockout mice indicated that 25-hydroxycholesterol (25HC) is synthesized by CYP27A1. Incubation of cholesterol or 25HC with mitochondrial and cytosolic fractions in the presence of 3 ¶-phosphoadenosyl 5 ¶-phosphosulfate resulted in the synthesis of 25HC3S. Real-time RT-PCR and Western blot analysis showed the presence of insulin-regulated hydroxycholesterol sulfotransferase 2B1b (SULT2B1b) in hepatocytes. 25HC3S, but not 25HC, decreased SULT2B1b mRNA and protein levels. Specific small interfering RNA decreased SULT2B1b mRNA, protein, and activity levels. These findings demonstrate that mitochondria synthesize 25HC, which is subsequently 3b-sulfated to form 25HC3S.-Li, X., W. M. Pandak, S. K. Erickson, Y. Ma, L. Yin, P. Hylemon, and S. Ren. Biosynthesis of the regulatory oxysterol, 5-cholesten-3b,25-diol 3-sulfate, in hepatocytes.

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Section: Discussionmentioning

confidence: 99%

Biosynthesis of the regulatory oxysterol, 5-cholesten-3β,25-diol 3-sulfate, in hepatocytes

Pandak

Erickson

et al. 2007

Journal of Lipid Research

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“…Early studies reported that quercetin, genistein, daidzein, and other flavonoids inhibited hepatic ETS, with quercetin being the most potent phytoestrogen (Huang et al 1997). In contrast, daidzein was reported to have no effect on ETS although sulfoconjugates of this phytoestrogen inhibited ETS (Wong & Keung 1997, Harris et al 2004. The effects of several dietary flavonoids, including quercetin, genistein, daidzein, and equol, on sulfotransferases have also been investigated and they inhibited hepatic oestrogen/androgen sulfotransferase with IC 50s in the nanomolar range (Ghazali & Waring 1999, Mesia-Vela & Kauffman 2003, Harris et al 2004.…”

Section: Phytoestrogens Oestrone Sulfatase and Sulfotransferasementioning

confidence: 99%

Phytoestrogens and breast cancer –promoters or protectors?

Rice¹,

Whitehead²

2006

Endocr Relat Cancer

165

119

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The majority of breast cancers are oestrogen dependent and in postmenopausal women the supply of oestrogens in breast tissue is derived from the peripheral conversion of circulating androgens. There is, however, a paradox concerning the epidemiology of breast cancer and the dietary intake of phytoestrogens that bind weakly to oestrogen receptors and initiate oestrogendependent transcription. In Eastern countries, such as Japan, the incidence of breast cancer is approximately one-third that of Western countries whilst their high dietary intake of phytoestrogens, mainly in the form of soy products, can produce circulating levels of phytoestrogens that are known experimentally to have oestrogenic effects. Indeed, their weak oestrogenicity has been used to advantage by herbalist medicine to promote soy products as a natural alternative to conventional hormone replacement therapy (HRT). Such usage could increase in light of recent evidence that long-term HRT usage may be associated with an increased risk of breast cancer with a consequent reduction in prescription rates. So, are phytoestrogens safe as a natural alternative to HRT and could they be promoters or protectors of breast cancer? If they are promoters, then we must assume that it is due to their oestrogenic effect. If they are protectors, then other actions of phytoestrogens, including their ability to inhibit enzymes that are responsible for converting androgens and weak oestrogens into oestradiol, must be considered. This paper addresses these questions by reviewing the actions of phytoestrogens on oestrogen receptors and key enzymes that convert androgens to oestrogens in relation to the growth of breast cancer cells. In addition, it compares the experimental and epidemiological evidence pertinent to the potential beneficial or harmful effects of phytoestrogens in relation to the incidence/progression of breast cancer and their efficacy as natural alternatives to conventional HRT.

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“…It is known that aglycones such as Dein and Gein, as well as equol, a metabolite of Dein, have biological effects such as a much higher affinity for estrogen receptor-␤ than for estrogen receptor-␣ (Kuiper et al, 1998;Nikov et al, 2000), inhibitory activity against topoisomerase II, and antioxidant activity (Arora et al, 1998;McCue and Shetty, 2004). In addition, many reports have been published describing the pharmacological or physiological effects of isoflavone conjugated metabolites, such as the inhibitory effect of daidzein-4Ј,7-disulfate (D-4Ј,7-diS) on sterol sulfatase in hamster liver microsomes (Wong and Keung, 1997), the stimulatory effect of daidzein-7-glucuronide-4Ј-sulfate (D-7G-4ЈS) on the growth of MCF-7 cells (Kinjo et al, 2004), the hypotensive and vasodilator effects of Dein sulfates in rats (Cao et al, 2006), and the weak estrogenic activity of Dein and Gein glucuronides (Zhang et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Metabolism and Disposition of Isoflavone Conjugated Metabolites in Humans after Ingestion of Kinako

Hosoda¹,

Furuta²,

Ishii³

2011

Drug Metab Dispos

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ABSTRACT:Isoflavone aglycones daidzein (Dein) and genistein (Gein) are present primarily as glucuronides and sulfates in human plasma; however, very little is known about the plasma pharmacokinetics of isoflavone conjugates after soy ingestion. The aim of this study was to investigate metabolism and disposition of the isoflavone conjugated metabolites glucuronide or sulfate or both after ingestion of kinako (

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Daidzein Sulfoconjugates Are Potent Inhibitors of Sterol Sulfatase (EC 3.1.6.2)

Cited by 80 publications

References 25 publications

Biosynthesis of the regulatory oxysterol, 5-cholesten-3β,25-diol 3-sulfate, in hepatocytes

Biosynthesis of the regulatory oxysterol, 5-cholesten-3β,25-diol 3-sulfate, in hepatocytes

Phytoestrogens and breast cancer –promoters or protectors?

Metabolism and Disposition of Isoflavone Conjugated Metabolites in Humans after Ingestion of Kinako

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