Estrogen Activities and the Cellular Effects of Natural Progesterone from Wild Yam Extract in MCF-7 Human Breast Cancer Cells

Park, Mi-Kyung; Kwon, Hyeok Yi; Ahn, Woong‐Shick; Bae, Su-Mi; Rhyu, Mee-Ra; Lee, Young‐Joo

doi:10.1142/s0192415x09006746

Cited by 22 publications

(22 citation statements)

References 27 publications

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“…ERα protein levels in the uterine tissues were down regulated after treatments with 0.003 mg/kg of E2. It is known that E2 downregulates ERα protein levels in MCF-7 cells, which is consistent with our result in uterus (Gierthy et al ., 1996; Park et al ., 2009). The 100 or 500 mg/kg of LNE significantly reduced the expression of ERα, PR-A and PR-B, compared with that of the E2-treated group in uterus (Fig.…”

Section: Resultsmentioning

confidence: 99%

Selective Estrogen Receptor Modulation by Larrea nitida on MCF-7 Cell Proliferation and Immature Rat Uterus

Ahn

Jeong

Bae

et al. 2014

Biomolecules & Therapeutics

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Larrea nitida is a plant that belongs to the Zygophyllaceae family and is widely used in South America to treat inflammatory diseases, tumors and menstrual pain. However, its pharmacological activity remains unclear. In this study we evaluated the property of selective estrogen receptor modulator (SERM) of Larrea nitida extracts (LNE) as a phytoestrogen that can mimic, modulate or disrupt the actions of endogenous estrogens, depending on the tissue and relative amount of other SERMs. To investigate the property of SERM of LNE, we performed MCF-7 cell proliferation assays, estrogen response element (ERE)-luciferase reporter gene assay, human estrogen receptor (hER) binding assays and in vivo uterotrophic assay. To gain insight into the active principles, we performed a bioassay-guided analysis of LNE employing solvents of various polarities and using classical column chromatography, which yielded 16 fractions (LNs). LNE showed high binding affinities for hERα and hERβ with IC50 values of 1.20 ×10−7 g/ml and 1.00×10−7 g/ml, respectively. LNE induced 17β-estradiol (E2)-induced MCF-7 cell proliferation, however, it reduced the proliferation in the presence of E2. Furthermore, LNE had an atrophic effect in the uterus of immature rats through reducing the expression level of progesterone receptor (PR) proteins. LN08 and LN10 had more potent affinities for binding on hER α and β than other fractions. Our results indicate that LNE had higher binding affinities for hERβ than hERα, and showed SERM properties in MCF-7 breast cancer cells and the rat uterus. LNE may be useful for the treatment of estrogen-related conditions, such as female cancers and menopause.

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Section: Resultsmentioning

confidence: 99%

Selective Estrogen Receptor Modulation by Larrea nitida on MCF-7 Cell Proliferation and Immature Rat Uterus

Ahn

Jeong

Bae

et al. 2014

Biomolecules & Therapeutics

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“…Dioscorea is proven to have antioxidative as well as antitumour properties 13, 14, 19. The antiproliferative activity of polyphenols such as delphinidin, cyanidin, peonidin, petunidin and malvidin has also been reported 20.…”

Section: Discussionmentioning

confidence: 99%

“…Dioscorin, polysaccharides, flavones, vitamin C and polyphenols of dioscorea have been proven to exhibit high antioxidative ability 12. In addition, dioscorea shows antitumour activity 13, 14. Thus Monascus fermentation of dioscorea should strengthen the anticancer effects of RMD.…”

Section: Introductionmentioning

confidence: 99%

Red mold dioscorea-induced G2/M arrest and apoptosis in human oral cancer cells

Hsu

Lee

Pan

2010

J. Sci. Food Agric.

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“…11.3), but also indicate the ability of WYRE to induce GATA3 mRNA in both ER + and ER − cell lines. A previous study also demonstrated that inhibition of MCF-7 (ER + ) cell proliferation by WYRE was the result of downregulation of ERα expression (Park et al 2009). Therefore, we predict that, WYRE is able to enhance GATA3 mRNA expression either by downregulating ER as in ER + cells (MCF-7) or by modulating hypermethylated GATA3 gene promoter as in ER − MDA-MB-231 cells.…”

Section: Discussionmentioning

confidence: 91%

“…To our knowledge, 14 steroidal saponins, 2 flavan-3-ol glycosides, and 14 diarylheptanoids have been reported from wild yam (Sautour et al 2006;Dong et al 2007;Hayes et al 2007;Yoon et al 2010;Ali et al 2013); among them diosgenin and dioscin exhibit anticancer activity (Jagadeesan et al 2012). WYRE was able to reduce cell proliferation, increase the expression of progesterone receptor and pS2 mRNA and down regulate ERα protein (Park et al 2009). Moreover, diosgenin (a steroidal saponin), have the potential to stimulate the growth of mammary epithelium of ovariectomized mice (Aradhana et al 1992) and effectively suppress fatty acid synthase expression in HER2overexpressing breast cancer cells (Chiang et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of wild yam (Dioscorea villosa) root extract as a potential epigenetic agent in breast cancer cells

Aumsuwan

Khan

et al. 2014

In Vitro Cell.Dev.Biol.-Animal

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The present study was designed to evaluate the efficacy of wild yam root extract (WYRE) as a potential demethylating agent using two breast cancer cell lines, MCF-7 (estrogen receptor positive; ER(+)) and MDA-MB-231 (Estrogen receptor negative; ER(-)), and a methylated gene, GATA3, as a potential marker of breast cancer development. The cells were treated with WYRE (0-50 μg/mL) for 72 h and used for viability, mRNA, and methylation analyses. WYRE significantly reduced viability of both cell lines and enhanced mRNA content of GATA3 in a concentration-dependent manner; however, DNMT mRNAs (DNMT1, 3A, 3B) were found to increase significantly only in MDA-MB-231 cells. Global DNA methylation, analyzed as 5'-methyl-2'-deoxycytidine (5-mC) and 5-hydroxymethylcytosine (5-hmC), showed a concentration-dependent enhancement of 5-mC with no alteration in 5-hmC level in MCF-7 cells; however, in MDA-MB-231 cells, in contrast to MCF-7 cells, 5-mC remained unaltered but 5-hmC reduced significantly in all WYRE concentrations (10-50 μg/mL) used in this study. Since 5-hmC is generated from 5-mC by ten-eleven-translocation (TET) enzymes, analysis of TET mRNAs (TET1, TET2, and TET3) in MDA-MB-231 cells indicated a concentration-dependent reduction in TET1 and induction of TET3; however, TET2 remained unaltered. No alterations in any of the TET mRNAs were found in MCF-7 cells. Methylation analysis of GATA3 promoter at specific locus indicates probable demethylating activity of WYRE in MDA-MB-231 cells. We conclude that activation of GATA3 gene in ER(-) MDA-MB-231 cells may occur by altering DNA methylation pattern on the promoter region which may be different from the mechanisms operated in ER(+) MCF-7 cells.

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Estrogen Activities and the Cellular Effects of Natural Progesterone from Wild Yam Extract in MCF-7 Human Breast Cancer Cells

Cited by 22 publications

References 27 publications

Selective Estrogen Receptor Modulation by Larrea nitida on MCF-7 Cell Proliferation and Immature Rat Uterus

Selective Estrogen Receptor Modulation by Larrea nitida on MCF-7 Cell Proliferation and Immature Rat Uterus

Red mold dioscorea-induced G2/M arrest and apoptosis in human oral cancer cells

Evaluation of wild yam (Dioscorea villosa) root extract as a potential epigenetic agent in breast cancer cells

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