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The effects of black cohosh on the regulation of estrogen receptor (ERα) and progesterone receptor (PR) in breast cancer cells

Authors Szmyd M, Lloyd V, Hallman K, Aleck K, Mladenovik V, McKee C, Morse M, Bedgood T, Dinda S

Received 26 June 2017

Accepted for publication 9 October 2017

Published 18 January 2018 Volume 2018:10 Pages 1—11


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Professor Pranela Rameshwar

Monica Szmyd,1–3 Victoria Lloyd,1–3 Kelly Hallman,1–3 Katie Aleck,1–3 Viktoria Mladenovik,1–3 Christina McKee,1–3 Mia Morse,1–3 Tyler Bedgood,1–3 Sumi Dinda1–3

1Biomedical and Therapeutic Sciences, School of Health Sciences, 2Prevention Research Center, 3Center of Biomedical Sciences, Oakland University, Rochester, MI, USA

Abstract: The North American plant Cimicifuga racemosa, also known as black cohosh (BC), is a herb that recently has gained attention for its hormonal effects. As the usage of hormone replacement therapy is declining due to its adverse effects in women with cancer, many are turning to herbal remedies like BC to treat menopausal symptoms. It is crucial to determine whether the effects of BC involve estrogen receptor-alpha (ERα). Previous studies from our laboratory have shown ERα to be a possible molecular target for BC. In this study, we examined the effects of BC (8% triterpene glycosides) alone and in combination with hormones and antihormones on the cellular viability, expression of ERα and progesterone receptor (PR)-A/B, and cytolocalization of ERα in ER (+) and PR-A/B (+) T-47D breast cancer cells. Cells were cultured and proteins were extracted and quantified. Western blot analysis revealed alterations in the expression of ERα and PR after treatment with BC (5–100 µM). BC induced a concentration-dependent decrease in ERα and PR protein levels when compared to the control. Image cytometric analysis with propidium iodide staining was used to enumerate changes in T-47D cell number and viability. A decrease in T-47D cell viability was observed upon treatment with 5–100 µM BC. The ideal concentration of BC (100 μM) was used in combination with hormones and antihormones in an effort to further understand the possible similarities between this compound and other known effectors of ERα and PR. After a 24-hour concomitant treatment with and/or in combination of BC, estradiol, ICI 182, 780, and Tamoxifen, downregulation of ERα and PR protein levels was observed. Delineating the role of BC in the regulation of ERα, PR, as well as its mechanisms of action, may be important in understanding the influence of BC on hormone receptors in breast cancer.

Keywords: black cohosh, breast cancer, ERα, progesterone receptor, hormone replacement therapy

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