Germacrone Inhibits Estrogen Receptor α‐Mediated Transcription in MCF‐7 Breast Cancer Cells

Abstract

Estrogen receptor (ER)α-positive breast cancer cells regulate the expression of estrogen-responsive genes, which are involved in cell proliferation, differentiation, and cell cycle progression. Clinically, the inhibition of ERα-mediated gene expression in breast cancer cells has long been considered an effective way to prevent the development and progression of cancer. Germacrone, a terpenoid compound isolated from Rhizoma curcuma, has been known to have antitumor activity in various human cancer cell lines. However, the mechanism by which germacrone inhibits the proliferation of breast cancer cells is still unclear. Here, we demonstrated that germacrone inhibits ERα-mediated gene expression at the transcriptional level in MCF-7 cells. Germacrone inhibits the recruitment of ERα to the estrogen response element on chromatin and consequently compromises the binding of switch/sucrose non-fermentable chromatin remodeling complex and RNA polymerase II to target gene promoter, thereby inhibiting the estrogen-induced chromatin accessibility. In addition, germacrone efficiently potentiates the antitumor activity of methotrexate and 5-fluorouracil. Our results not only provide substantial molecular mechanism of germacrone on ERα-mediated signaling in breast cancer cells but also demonstrate the benefits of germacrone as a combination therapy with other drugs for the treatment of breast cancer. Copyright © 2016 John Wiley & Sons, Ltd.

Germacrone protects against oxygen-glucose deprivation/reperfusion injury by inhibiting autophagy processes in PC12 cells

“…Recent studies have found that germacrone has a significant anti-cancer effect, can inhibit the progress of colorectal cancer, liver cancer, breast cancer, lung cancer and other cancers, and has the characteristics of high efficiency and low toxicity [18][19][20]. Lim et al found that germacrone inhibited breast cancer progression by inhibiting estrogen receptor α and synergizing with other antitumor drugs 5-fluorouracil and methotrexate [21]. However, there are relatively few studies on the neuroprotective effects of germacrone.…”

Predicted molecular targets and pathways for germacrone, curdione, and furanodiene in the treatment of breast cancer using a bioinformatics approach

“…As an alternative treatment for breast cancer, ingredients isolated from natural products have been extensively investigated. In our previous study, we showed that germacrone inhibits the proliferation and migration of MCF-7 breast cancer cells 5 by the inhibition of ERα signaling 24 . The expressions of the anti-apoptotic Bcl-2 and Bcl-xL protein and the pro-apoptotic TP53 and TP21 were dose-dependently regulated by germacrone as well 25 – 27 .…”

Antiviral Activity of Germacrone against Pseudorabies Virus in Vitro

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