Publications by authors named "Bilan Mo"

4 Publications

  • Page 1 of 1

Characterization of antiestrogenic activity of the Chinese herb, prunella vulgaris, using in vitro and in vivo (Mouse Xenograft) models.

Biol Reprod 2009 Feb 15;80(2):375-83. Epub 2008 Oct 15.

Department of Obstetrics and Gynecology, Greenville Hospital System, Greenville, South Carolina 29605, USA.

Prunella vulgaris (PV), a commonly used Chinese herb, also known as Self-heal, has a wide range of reported medicinal activities. By screening multiple herbs using the endometrial cancer cell line, ECC-1, and an alkaline phosphatase detection assay, we found that PV displayed significant antiestrogenic activity. We investigated the possible usefulness of antiestrogenic activity using both in vitro and in vivo models of endometrial function. Using the well-differentiated, hormone-responsive endometrial cell line, ECC-1, PV extract, at concentrations that were not toxic to the cells, significantly reduced alkaline phosphatase activity and cell proliferation in response to estrogen in a dose-dependent manner. The expression of CYR61, an estrogen-induced protein, was blocked in ECC-1 cells by both the antiestrogen ICI 182,780 and PV extract. Interestingly, PV extract did not appear to directly inhibit estrogen signaling. Rather, we found that its activities were probably related to an ability to function as an aryl hydrocarbon receptor (AHR) agonist in ECC-1 cells. In support of this hypothesis, we noted that PV induced CYP1A1, CYP1B1, and AHR repressor expression in a dose-dependent manner--responses that were blocked by small interfering RNA treatment to reduce AHR and specific AHR antagonists. Ovariectomized immunodeficient RAG-2/gamma(c) knockout mice implanted with human endometrial xenografts developed implants only when treated with estrogen. Mice treated with estrogen and PV tea in their drinking water had fewer and smaller xenograft implants compared with their estrogen-treated counterparts that drank only water (P < 0.05). Analysis of the resulting implants by immunohistochemistry demonstrated persistent estrogen receptor (ER), but reduced proliferation and CYR61 expression. Mouse uterine tissue weight in PV-treated mice was not different from controls, and cycle fecundity of intact C57 female mice was unaffected by PV tea treatment. PV, or Self-heal, exhibits significant antiestrogenic properties, both in vitro and in vivo. This activity is likely due to the ability of PV-activated AHR to interfere with estrogen. This herb may be useful as an adjunct for the treatment of estrogen-dependent processes like endometriosis and breast and uterine cancers. Full characterization of this herb will likely provide new insights into the crosstalk between AHR and ESR1, with potential for therapeutic applications in women.
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http://dx.doi.org/10.1095/biolreprod.107.065375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746405PMC
February 2009

Endometrial expression of Cyr61: a marker of estrogenic activity in normal and abnormal endometrium.

Obstet Gynecol 2007 Jul;110(1):146-54

Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.

Objective: To compare the expression of Cyr61 in normal cycling endometrium with endometrium from women with polycystic ovarian syndrome (PCOS) and endometrial hyperplasia and adenocarcinoma.

Methods: This is a retrospective study of 59 samples of normal and abnormal endometrium. Endometrial biopsies were obtained from normal fertile controls throughout the menstrual cycle and compared with endometrium from ovulatory and anovulatory women with PCOS and complex endometrial hyperplasia and endometrioid adenocarcinoma. Cyr61 expression was evaluated by using immunohistochemistry and reverse transcription PCR for Cyr61, estrogen receptor (ER)-alpha, a marker of cell proliferation (Ki67), and another marker of early estrogen action, cFos. Regulation of Cyr61 protein was studied in a steroid-responsive endometrial carcinoma cell line, ECC1.

Results: Cyr61 protein was regulated by estrogen. In normal endometrium, Cyr61 was highest in the proliferative phase and lowest in the normal midsecretory phase. In contrast, elevated levels of Cyr61, ER-alpha, Ki67, and cFos were all found in the midsecretory endometrium of ovulatory PCOS patients, endometrial cancer patients, and hyperplasia patients.

Conclusion: Cyr61 is overexpressed in PCOS endometrium, reflecting a heightened responsiveness to estrogen. As a unique marker of estrogen action, Cyr61 may be an early biomarker for the development of hyperplasia or adenocarcinoma in this group of women.
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http://dx.doi.org/10.1097/01.AOG.0000269047.46078.28DOI Listing
July 2007

ECC-1 cells: a well-differentiated steroid-responsive endometrial cell line with characteristics of luminal epithelium.

Biol Reprod 2006 Sep 17;75(3):387-94. Epub 2006 May 17.

Center for Women's Medicine, Division of Reproductive Endocrinology and Infertility, Greenville Hospital System, Greenville, South Carolina 29605, USA.

Endometrial cancer cell lines have provided a valuable model to study endometrial epithelial cells in vitro. Since the first development of HEC1B over 35 yr ago, many different cell lines have been isolated and described. One valuable cell line that maintains hormone responsiveness and unique stability over time is the ECC-1 cell line, developed originally by the late P.G. Satyaswaroop. In this study, we investigated some of the properties of these cells and present their salient characteristics. Like Ishikawa cells, ECC-1 cells maintain both estrogen receptors (ESR1 [ER alpha] and ESR2 [ER beta]), progesterone receptors (PR A and B; PGRs), and androgen receptors (ARs), along with the p160 steroid receptor coactivators NCOA1 (formerly SRC1), NCOA2 (formerly TIF2), and NCOA3 (formerly AIB1). The karyotype of these cells is abnormal, with multiple structural rearrangements in all cells analyzed. Unlike Ishikawa cells that express glandular epithelial antigens, ECC-1 cells maintain a luminal phenotype, with expression of KRT13 (cytokeratin 13) and KRT18 (cytokeratin 18). Apparent differences in the regulation of ESR2 also were evident in ECC-1 cells compared to Ishikawa cells. Like other endometrial cell lines, ECC-1 cells express the steroid receptor coactivators and exhibit epidermal growth factor-stimulated expression of known luminal proteins thought to be involved in implantation, including the hyaluronate receptor CD44 and SPP1 (formerly osteopontin) and CD55 (decay-accelerating factor). These characteristics appear to be stable and persistent over multiple cell passages, making this well-differentiated cell line an excellent choice to study endocrine and paracrine regulation of endometrial epithelium in vitro.
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http://dx.doi.org/10.1095/biolreprod.106.051870DOI Listing
September 2006

Apoptosis, 5-fluorouracil sensitivity and expression of apoptotic proteins in a human ectocervical cell carcinogenesis model using different media.

Authors:
Bilan Mo Alan Pater

Eur J Pharmacol 2003 Apr;467(1-3):15-22

Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philip Drive, St. John's, Newfoundland, Canada A1B 3V6.

Apoptosis has received widespread attention for its essential roles in biology, medicine and cancer. We previously found that normal, human papillomavirus (HPV) 16-immortalized and their transformed endocervical cells were increasingly resistant to apoptosis induced by a cancer therapeutic drug. Here, analogously, another common anticancer drug, 5-fluorouracil, in an ectocervical cell carcinogenesis model induced apoptosis in primary human ectocervical cells (HEC), whereas HPV18-immortalized HEC (HEC-18) and transformed HEC-18 (HEC-18T) were more resistant. Growth in serum/low density lipoprotein (LDL)-containing medium reversed resistance to 5-fluorouracil-induced apoptosis, particularly in HEC-18T. Cell viability results confirmed these findings. Using Western blots to compare protein levels with those of HEC not treated with 5-fluorouracil, the fold changes in HEC-18 and HEC-18T in LDL-free medium were 1.6-6.1-fold lower for pro-apoptotic p53, Bak and Bax. Four anti-apoptotic proteins were altered -2.1 to+14.6-fold for Bcl-2 and BAG-1 isoform p33 and p29. For BAG-1 p50 and p46, HEC-18 were weakly expressed and HEC-18T were moderately higher. Grown in LDL-containing medium, the differences in pro-apoptotic protein levels were mostly reversed. Expression was 1.4-32-fold higher in HEC-18 and HEC-18T of p53, Bax, BAG-1 p29, BAG-1 p33 and total BAG-1. These results showed that HEC carcinogenesis results in resistance to 5-fluorouracil-induced apoptosis, associated with reduced expression during carcinogenesis of pro-apoptotic proteins and increased expression of specific anti-apoptotic proteins.
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http://dx.doi.org/10.1016/s0014-2999(03)01561-9DOI Listing
April 2003