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

Publication ,  Journal Article
Collins, NH; Lessey, EC; DuSell, CD; McDonnell, DP; Fowler, L; Palomino, WA; Illera, MJ; Yu, X; Mo, B; Houwing, AM; Lessey, BA
Published in: Biol Reprod
February 2009

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.

Duke Scholars

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Published In

Biol Reprod

DOI

ISSN

0006-3363

Publication Date

February 2009

Volume

80

Issue

2

Start / End Page

375 / 383

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Receptors, Aryl Hydrocarbon
  • Prunella
  • Protein Binding
  • Plant Extracts
  • Obstetrics & Reproductive Medicine
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
 

Citation

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Collins, N. H., Lessey, E. C., DuSell, C. D., McDonnell, D. P., Fowler, L., Palomino, W. A., … Lessey, B. A. (2009). Characterization of antiestrogenic activity of the Chinese herb, prunella vulgaris, using in vitro and in vivo (Mouse Xenograft) models. Biol Reprod, 80(2), 375–383. https://doi.org/10.1095/biolreprod.107.065375
Collins, Nancy H., Elizabeth C. Lessey, Carolyn D. DuSell, Donald P. McDonnell, Lindsay Fowler, Wilder A. Palomino, Maria J. Illera, et al. “Characterization of antiestrogenic activity of the Chinese herb, prunella vulgaris, using in vitro and in vivo (Mouse Xenograft) models.Biol Reprod 80, no. 2 (February 2009): 375–83. https://doi.org/10.1095/biolreprod.107.065375.
Collins NH, Lessey EC, DuSell CD, McDonnell DP, Fowler L, Palomino WA, et al. Characterization of antiestrogenic activity of the Chinese herb, prunella vulgaris, using in vitro and in vivo (Mouse Xenograft) models. Biol Reprod. 2009 Feb;80(2):375–83.
Collins, Nancy H., et al. “Characterization of antiestrogenic activity of the Chinese herb, prunella vulgaris, using in vitro and in vivo (Mouse Xenograft) models.Biol Reprod, vol. 80, no. 2, Feb. 2009, pp. 375–83. Pubmed, doi:10.1095/biolreprod.107.065375.
Collins NH, Lessey EC, DuSell CD, McDonnell DP, Fowler L, Palomino WA, Illera MJ, Yu X, Mo B, Houwing AM, Lessey BA. Characterization of antiestrogenic activity of the Chinese herb, prunella vulgaris, using in vitro and in vivo (Mouse Xenograft) models. Biol Reprod. 2009 Feb;80(2):375–383.

Published In

Biol Reprod

DOI

ISSN

0006-3363

Publication Date

February 2009

Volume

80

Issue

2

Start / End Page

375 / 383

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Receptors, Aryl Hydrocarbon
  • Prunella
  • Protein Binding
  • Plant Extracts
  • Obstetrics & Reproductive Medicine
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice