Estrogenic Activity of Hyperforin in MCF-7 Human Breast Cancer Cells Transfected with Estrogen Receptor

Abstract

Hyperforin, a major active compound of St.?John?s wort extract, affects estrogenic activity. In this study, the compound evoked estrogen response element-dependent luciferase activity and cell proliferation in MCF-7 cells. Hyperforin-induced cell proliferation was significantly inhibited by the estrogen receptor antagonist ICI 182,780. These results suggested that hyperforin had estrogenic and cell proliferation activities, which were stimulated via the estrogen receptor. Compared to 17?-estradiol, hyperforin showed significantly lower estrogenic activity and cell proliferation. The mechanism underlying the estrogenic activity of hyperforin was unknown, therefore, in this study, for the first time, the expression and post-translational modification of proteins were determined and compared among control, 17?-estradiol-treated, and hyperforin-treated cells using proteomic techniques. A total of 453 proteins were identified, of which 282 proteins were significantly modulated in hyperforin-treated cells compared to 17?-estradiol-treated cells. Ingenuity pathway analysis also demonstrated that hyperforin treatment induced less cell proliferation than 17?-estradiol by downregulating estrogen receptor 1. Protein network analysis showed that cell proliferation was regulated mainly by cyclin D1 and extracellular signal-regulated kinases. In conclusion, although, hyperforin exhibited lower estrogenic activity than 17?-estradiol, the compound induced lower levels of cancer cell proliferation in vitro.

Safety Assessment of Endocrine Disruption by Menopausal Health Functional Ingredients

“…Estrogenic and cell-proliferative activities of SJW extract and its major bioactive compound HF were reported in an experimental study; SJW and HF increased luciferase activity in MCF-7 cells transfected with ERα or ERβ (Figure 4) [58]. The binding of SJW and HF to ERα, and the binding of SJW to ERβ, are shown in Figure 4a-d.…”

“…The binding of SJW and HF to ERα, and the binding of SJW to ERβ, are shown in Figure 4a-d. Although HF treatment induced lower breast cancer cell proliferation than 17β-E2 treatment in vitro [58], data on the long-term effect of SJW on the risk of breast cancer, which is a health-related major concern of middle-aged women, are still insufficient.…”

“…Studies on each functional ingredient, individually approved ingredients, and herbal medicine about estrogen receptor binding activity are summarized in Table 1. [57] Black cohosh MCF-7 cell + Kwon et al (2016) [58] St. John's wort MCF-7 cell + Cho et al ( 2004) [59] Ginsenoside-Rb1 Black cohosh is an herb native to eastern North America that has a history of traditional use among Native Americans for the treatment of various symptoms in women, including menopausal symptoms. In clinical studies conducted in Asia and Europe, black cohosh extract was shown to be effective in relieving symptoms in women with menopausal symptoms and is efficacious as tibolone, a hormone preparation [69,70].…”

“…St. John's wort (SJW) is widely used with therapeutic effects on depression, relieving psychological and psychosomatic symptoms such as anxiety and insomnia of menopause, and having an anti-inflammatory effect [58,80]. SJW is known to contain various antidepressant-related components including hyperforin (HF), flavonoids, xanthones, and bioflavonoids [81].…”

Research Progress of Polycyclic Polyprenylated Acylphloroglucinols

“…Hyperforin ( 422 ) has been also shown to display antibacterial, ,, antioxidant, antimalarial, larvicidal, and estrogenic activities in the time range of this review …”