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Journal ArticleDOI

Estrogenic Activity of Sanguiin H-6 through Activation of Estrogen Receptor α Coactivator-binding Site

31 Mar 2019-Natural product sciences (The Korean Society of Pharmacognosy)-Vol. 25, Iss: 1, pp 28-33
TL;DR: Phytochemicals from Rubus coreanus that were able to disrupt ERα and coactivator interaction with an ERα antagonist were investigated and indicated that sanguiin H6 contributed to the estrogenic activity of R. coreanus through the activation of the ERα coActivator-binding site.
Abstract: A popular approach for the study of estrogen receptor α inhibition is to investigate the protein-protein interaction between the estrogen receptor (ER) and the coactivator surface. In our study, we investigated phytochemicals from Rubus coreanus that were able to disrupt ERα and coactivator interaction with an ERα antagonist. The E-screen assay and molecular docking analysis were performed to evaluate the effects of the estrogenic activity of R. coreanus extract and its constituents on the MCF-7 human breast cancer cell line. At 100 μg/mL, R. coreanus extract significantly stimulated cell proliferation (574.57 ± 8.56%). Sanguiin H6, which was isolated from R. coreanus, demonstrated the strongest affinity for the ERα coactivator-binding site in molecular docking analysis, with a binding energy of -250.149. The initial results of the study indicated that sanguiin H6 contributed to the estrogenic activity of R. coreanus through the activation of the ERα coactivator-binding site.

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TL;DR: The study of a Hawaiian volcanic soil-associated fungal strain Penicillium herquei FT729 led to the isolation of one unprecedented benzoquinone-chromanone, herqueilenone A and two phenalenone derivatives, whose structures were determined through extensive analysis of NMR spectroscopic data and gauge-including atomic orbital (GIAO) NMR chemical shifts and ECD calculations.

32 citations

Journal ArticleDOI
TL;DR: The isolation of a novel sterol, calvatianone, possessing a 6/5/6/5-fused ring system with a contracted tetrahydrofuran B-ring, and four known steroids from the fruiting bodies of C. nipponica is reported.
Abstract: Calvatia nipponica is an extremely rare mushroom with a limited number of studies on its chemical components and biological activities published. Here we report the isolation of a novel sterol, calvatianone (1), possessing a 6/5/6/5-fused ring system with a contracted tetrahydrofuran B-ring, and four known steroids (2-5) from the fruiting bodies of C. nipponica. The structure of calvatianone including its absolute configuration was determined by NMR spectroscopic analyses, HR-ESIMS, gauge-including atomic orbital NMR chemical shift calculations, and ECD calculations. Ergosterol peroxide (3) and cyathisterol (4) suppressed the cell viability increase induced by 17β-estradiol in MCF-7 breast cancer cell lines, suggesting a possible approach for these compounds to serve as ERα antagonists.

25 citations

Journal ArticleDOI
TL;DR: In this paper, two new coumaric acid-aliphatic alcohol hybrids, ginkwanghols A (1) and B (2), were isolated from the leaves of G. biloba.
Abstract: Ginkgo biloba (Ginkgoaceae), commonly known as "ginkgo", is called a living fossil, and it has been cultivated early in human history for various uses in traditional medicine and as a source of food. As part of ongoing research to explore the chemical diversity and biologically active compounds from natural resources, two new coumaric acid-aliphatic alcohol hybrids, ginkwanghols A (1) and B (2) were isolated from the leaves of G. biloba. The coumaric acid-aliphatic alcohol hybrids of natural products have rarely been reported. The structures of the new compounds were determined by extensive NMR spectroscopic analysis, HRESI-MS, and quantum chemical ECD calculations, and by comparing the experimental HRESI-MS/MS spectrum of chemically transformed compound 1a with the predicted HRESI-MS/MS spectra proposed from CFM-ID 3.0, a software tool for MS/MS spectral prediction and MS-based compound identification. Ginkwanghols A (1) and B (2) increased alkaline phosphatase (ALP) production in C3H10T1/2, a mouse mesenchymal stem cell line, in a dose-dependent manner. In addition, ginkwanghols A and B mediated the promotion of osteogenic differentiation as indicated by the induction of the mRNA expression of the osteogenic markers ALP and osteopontin (OPN).

23 citations

Journal ArticleDOI
TL;DR: In this paper, the potential anti-skin aging effect of (-)-phenolic compounds isolated from the root bark of Ulmus davidiana var. japonica was evaluated, and (-)-catechin is a candidate to ameliorate both intrinsic and extrinsic skin aging.
Abstract: Reactive oxygen species (ROS) are generated during skin aging, including intrinsic (chronologic aging) and extrinsic aging (photoaging). Therefore, antioxidants that inhibit ROS generation can delay skin aging. In this study, we evaluated the potential anti-skin aging effect of (-)-phenolic compounds isolated from the root bark of Ulmus davidiana var. japonica. We preferentially investigated the possible preventive effects of isolates against the degradation of skin extracellular matrix. Among the isolates, (-)-catechin suppressed the activity of collagenase MMP-1, and reversed the degradation of collagen induced by tumor necrosis factor-α (TNF-α) in normal human dermal fibroblast. This action mechanism of (-)-catechin was validated by the suppression of tumor necrosis factor-α-induced accumulation of ROS and activation of mitogen-activated protein kinases, protein kinase B (Akt), and cyclooxygenase-2 (COX-2). The proinflammatory cytokines upregulate inflammatory reactions, and ultimately promote aging-related reactions. In this milieu, we demonstrated that (-)-catechin decreased the expression and secretion of proinflammatory cytokines, including interleukin (IL)-1β and IL-6. In conclusion, (-)-catechin is a candidate to ameliorate both intrinsic and extrinsic skin aging.

22 citations

Journal ArticleDOI
TL;DR: In this paper, the authors investigated the antidiabetic properties of the white mulberry (Morus alba) fruits using 3T3-L1 adipocytes and found that rutin and quercetin improved glucose uptake via Akt-mediated insulin signaling pathway or AMP-activated protein kinase (AMPK) activation.
Abstract: Morus alba (Moraceae), known as white mulberry, has been used to treat fever, protect against liver damage, improve eyesight, and lower blood sugar levels in traditional oriental medicine. Few studies have been conducted on the antidiabetic compounds identified from M. alba and their underlying mechanisms of action. Consequently, in this study, the fruits of M. alba were investigated for potential antidiabetic natural products using 3T3-L1 adipocytes. Phytochemical analysis of the ethanolic extract of M. alba fruits, followed by high-performance liquid chromatography (HPLC), purification led to the isolation of two main compounds: rutin and quercetin-3-O-β-d-glucoside (Q3G). Long-term use of available drugs for treating type 2 diabetes ((T2D) is often accompanied by undesirable side effects, which have generated increased interest in the development of more effective and safer antidiabetic agents. Examination of the isolated compounds, rutin and Q3G, for antidiabetic or anti-obesity properties or both in 3T3-L1 adipocytes demonstrated that they both improved glucose uptake via Akt-mediated insulin signaling pathway or AMP-activated protein kinase (AMPK) activation in 3T3-L1 adipocytes. The compounds also showed a positive effect on lipid accumulation in adipocytes, suggesting that glucose uptake occurred through activation of the Akt and AMPK signaling pathway without inducing adipogenesis. Taken together, our findings suggest that rutin and Q3G in M. alba fruits have the potential to induce fewer side effects such as weight gain, and these active compounds could be potential therapeutic candidates for the management of T2D.

18 citations

References
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Journal ArticleDOI
TL;DR: The aims of the work summarized in this paper were to validate the E-SCREEN assay, to screen a variety of chemicals present in the environment to identify those that may be causing reproductive effects in wildlife and humans, and to assess whether environmental estrogens may act cumulatively.
Abstract: Estrogens are defined by their ability to induce the proliferation of cells of the female genital tract. The wide chemical diversity of estrogenic compounds precludes an accurate prediction of estrogenic activity on the basis of chemical structure. Rodent bioassays are not suited for the large-scale screening of chemicals before their release into the environment because of their cost, complexity, and ethical concerns. The E-SCREEN assay was developed to assess the estrogenicity of environmental chemicals using the proliferative effect of estrogens on their target cells as an end point. This quantitative assay compares the cell number achieved by similar inocula of MCF-7 cells in the absence of estrogens (negative control) and in the presence of 17 beta-estradiol (positive control) and a range of concentrations of chemicals suspected to be estrogenic. Among the compounds tested, several "new" estrogens were found; alkylphenols, phthalates, some PCB congeners and hydroxylated PCBs, and the insecticides dieldrin, endosulfan, and toxaphene were estrogenic by the E-SCREEN assay. In addition, these compounds competed with estradiol for binding to the estrogen receptor and increased the levels of progesterone receptor and pS2 in MCF-7 cells, as expected from estrogen mimics. Recombinant human growth factors (bFGF, EGF, IGF-1) and insulin did not increase in cell yields. The aims of the work summarized in this paper were a) to validate the E-SCREEN assay; b) to screen a variety of chemicals present in the environment to identify those that may be causing reproductive effects in wildlife and humans; c) to assess whether environmental estrogens may act cumulatively; and finally d) to discuss the reliability of this and other assays to screen chemicals for their estrogenicity before they are released into the environment.

1,800 citations

Journal Article
TL;DR: Dietary genistein can act as an estrogen agonist in vivo and in vitro, resulting in the proliferation of cultured human breast cancer cells (MCF-7) and the induction of pS2 gene expression.
Abstract: Genistein, found in soy products, is a phytochemical with several biological activities. In the current study, our research focused on the estrogenic and proliferation-inducing activity of genistein. We have demonstrated that genistein enhanced the proliferation of estrogen-dependent human breast cancer (MCF-7) cells in vitro at concentrations as low as 10 nM, with a concentration of 100 nM achieving proliferative effects similar to those of 1 nM estradiol. Expression of the estrogen-responsive gene pS2 was also induced in MCF-7 cells in response to treatment with a concentration of genistein as low as 1 microM. At higher concentrations (above 20 microM), genistein inhibits MCF-7 cell growth. In vivo, we have shown that dietary treatment with genistein (750 ppm) for 5 days enhanced mammary gland growth in 28-day-old ovariectomized athymic mice, indicating that genistein acts as an estrogen in normal mammary tissue. To evaluate whether the estrogenic effects observed in vitro with MCF-7 cells could be reproduced in vivo, MCF-7 cells were implanted s.c. in ovariectomized athymic mice, and the growth of the estrogen-dependent tumors was measured weekly. Negative control animals received the American Institute of Nutrition (AIN)-93G diet, the positive control group received a new s.c. estradiol (2 mg) pellet plus the AIN-93G diet, and the third group received genistein at 750 ppm in the AIN-93G diet. Tumors were larger in the genistein (750 ppm)-treated group than they were in the negative control group, demonstrating that dietary genistein was able to enhance the growth of MCF-7 cell tumors in vivo. Increased uterine weights were also observed in the genistein-treated groups. In summary, genistein can act as an estrogen agonist in vivo and in vitro, resulting in the proliferation of cultured human breast cancer cells (MCF-7) and the induction of pS2 gene expression. Here we present new information that dietary genistein stimulates mammary gland growth and enhances the growth of MCF-7 cell tumors in ovariectomized athymic mice.

601 citations

Journal ArticleDOI
TL;DR: Age-standardized cancer incidence rates have decreased between 2011 and 2013; mortality rates have also declined since 2002, while 5-year survival rates have improved remarkably from 1993-1995 to 2009-2013 in Korea.
Abstract: Purpose: This study described the 2013 nationwide cancer statistics in Korea, including cancer incidence, survival, prevalence, and mortality.

427 citations

Journal ArticleDOI
TL;DR: The incidence rate of all cancers in Korea appears to have decreased mainly because of a decrease in thyroid cancer, and up-to-date estimates of the cancer burden in Korea could be an important resource for planning and evaluation of cancer-control programs.
Abstract: PURPOSE This study aimed to report on cancer incidence and mortality for the year 2017 in Korea in order to estimate the nation's current cancer burden. MATERIALS AND METHODS Cancer incidence data from 1999 to 2014 were obtained from the Korea National Cancer Incidence Database, and cancer mortality data from 1993 to 2015 were acquired from Statistics Korea. Cancer incidence and mortality were projected by fitting a linear regression model to observe age-specific cancer rates against observed years, and then multiplying the projected age-specific rates by the age-specific population. The Joinpoint regression model was used to determine at which year the linear trend changed significantly; we only used data of the latest trend. RESULTS A total of 221,143 new cancer cases and 80,268 cancer deaths are expected to occur in Korea in 2017. The most common cancer sites are the colorectum, stomach, lung, thyroid, and breast. These five cancers represent half of the overall burden of cancer in Korea. For mortality, the most common sites are the lung, liver, colorectal, stomach, and pancreas. CONCLUSION The incidence rate of all cancers in Korea appears to have decreased mainly because of a decrease in thyroid cancer. These up-to-date estimates of the cancer burden in Korea could be an important resource for planning and evaluation of cancer-control programs.

296 citations

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