Gene expression profiling reveals effects of Cimicifuga racemosa (L.) NUTT. (black cohosh) on the estrogen receptor positive human breast cancer cell line MCF-7

Gaube, Friedemann; Wölfl, Stefan; Pusch, Larissa; Kroll, Torsten; Hamburger, Matthias

doi:10.1186/1471-2210-7-11

Cited by 56 publications

(45 citation statements)

References 65 publications

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“…Authors have speculated that black cohosh may work through estrogen-like compounds 10 . However, today black cohosh is thought to reduce hot flushes by modulating the central dopaminergic and serotoninergic metabolism 11 , and not via steroid hormone receptors 12 .…”

Section: Introductionmentioning

confidence: 99%

The impact of testosterone, tibolone and black cohosh on purified mammary and placental 17β-hydroxysteroid dehydrogenase type 1

Stute

Kalkhake

Kiesel³

et al. 2014

Journal of Enzyme Inhibition and Medicinal Chemistry

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Context: Mammary and placental 17b-hydroxysteroid dehydrogenase type 1 (17bHSD1). Objective: To assess the impact of testosterone, tibolone, and black cohosh on purified mammary and placental 17bHSD1. Materials and methods: 17bHSD1 was purified from human mammary gland and placenta by column chromatography, its activity was monitored by a radioactive activity assay, and the degree of purification was determined by gel electrophoresis. Photometric cofactor transformation analysis was performed to assess 17bHSD1 activity without or in presence of testosterone, tibolone and black cohosh. Results: 17bHSD1 from both sources displayed a comparable basal activity. Testosterone and tibolone metabolites inhibited purified mammary and placental 17bHSD1 activity to a different extent, whereas black cohosh had no impact. Discussion: Studies on purified enzymes reveal the individual action of drugs on local regulatory mechanisms thus helping to develop more targeted therapeutic intervention. Conclusion: Testosterone, tibolone and black cohosh display a beneficial effect on local mammary estrogen metabolism by not affecting or decreasing local estradiol exposure.

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Section: Introductionmentioning

confidence: 99%

The impact of testosterone, tibolone and black cohosh on purified mammary and placental 17β-hydroxysteroid dehydrogenase type 1

Stute

Kalkhake

Kiesel³

et al. 2014

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…In addition there are reports about other active principles of black cohosh such as the biologically active constituents triterpene glycoside and cycloartane glycoside (Gaube et al, 2007;Kanadys et al, 2008). These named neocimigenosides A and B were isolated and identifi ed by chromatographic and spectroscopic analyses by Mimaki et al (2006).…”

Section: Discussionmentioning

confidence: 95%

Absence of positive effect of black cohosh (Cimicifuga racemosa) on fracture healing in osteopenic rodent model

Kolios

Daub

Sehmisch

et al. 2010

Phytotherapy Research

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The healing of predominantly metaphyseal fractures in postmenopausal osteoporosis is delayed and comparatively poor. Due to the potential side effects of HRT, natural alternatives are appealing. The aim of this study was to determine whether Cimicifuga racemosa extract BNO 1055 improves metaphyseal fracture healing in severe osteopenic bone in rats. Thirty-three 12-week-old female rats developed severe osteopenia during 10 weeks after ovariectomy. After metaphyseal tibial-osteotomy and standardized T-plate-osteosynthesis, the healing periods in ovariectomized rats (C), 17-α-estradiol (E) and Cimicifuga racemosa (CR) supplemented diets were assessed for 35 days. Changes in callus morphology were evaluated qualitatively by biomechanical testing and quantitatively in microradiographies and fluorochrome-labeled histological sections. The CR-supplementation slightly improved callus quality and trabecular bone formation. It significantly enhanced the endosteal callus density compared to C group (Cl.Dn.e C: 59.08 ± 21.89, E: 45.95 ± 18.39, CR: 60.85 ± 18.66*), though most of the other morphological parameters examined showed no improvement. The time course of fracture healing did not change due to CR. Estrogen-supplementation enhanced the biomechanical properties of the fracture site. Trabecular bone was improved indicating the physiological endosteal healing process. The CR-supplementation did not exhibit positive effects in severe (senile) osteopenic fracture healing as seen in early (postmenopausal) osteoporosis in rats. Callus formation was slightly improved under CR. Estrogen improved fracture healing in severe osteopenic bone, while the extent of callus formation played a minor role.

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“…Oral administration of iCR or E2 for 1 week to ovariectomized rats was able to restore neuronal excitability leading to functional recovery of hypothalamic activity [14,24]. Furthermore, iCR has been shown to upregulate genes related to cell survival under metabolic stress such as hypoxia [28][29][30]. In hypoestrogenic women, the cerebral blood flow has been shown to be reduced with regional patterns resembling those of patients with mild to moderate Alzheimer's disease [31].…”

Section: Discussionmentioning

confidence: 99%

Effects of black cohosh on estrogen biosynthesis in hippocampus of non-human primates ex vivo in vitro and in human neuroblastoma cells in vitro

et al. 2016

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Background: Estrogens have neuroprotective properties. The aim of the study was to assess the impact of an isopropanolic extract of Cimicifuga racemosa (iCR), 17ß-estradiol (E2), testosterone (T) and Tibolone's 3α-OH metabolite (Org4094) on local estrogen formation in hippocampus tissue from non-human primates ex vivo in vitro and human neuroblastoma cells (SH-SY5Y) in vitro. Methods: SH-SY5Y cells were incubated in RPMI 1640 medium containing 5 % steroid-depleted fetal calf serum for 3 days, and subsequently incubated in absence or presence of iCR at 10 μg/ml (n = 5) and 1 μg/ml (n = 5), E2 at 10 −8 M (n = 5), and 10 −6 M (n = 5), or T at 10 −8 M (n = 5), and 10 −6 M (n = 5), respectively, at 37°C for either 24 h or directly in cell extracts. Hippocampus tissue from healthy female cynomolgus macaques (n = 14) was homogenized and treated with iCR, E2 and Org4049 accordingly. STS activity was evaluated by incubating homogenized brain cells and tissue with [3H]-estrone sulfate and separating the products estrone (E1) and E2 by thin layer chromatography. STS activity was expressed as total estrogen formation (E1 + E2) fmol/mg of protein/min. Statistical comparisons were made using unpaired T-Test for comparing two sets of data and ANOVA to compare many groups at once. A p value < 0.05 was considered to be significant different. Results: Basal total estrogen formation was significantly higher in proliferative SH-SY5Y cells (1350.06 ± 109 E1 + E2 fmol/mg of protein/min) compared to hippocampus tissue (37.83 ± 3.9 E1 + E2 fmol/mg of protein/min; p < 0.01). ICR exerted a bidirectional action with an immediate strong inhibitory effect being followed by a stimulation of STS activity (85 % increase). E2 had a bidirectional dose-dependent long-term effect on STS activity (−23 % reduction and 18 % increase). T and Org4094 had an immediate strong inhibitory effect on STS activity that further maintained with 24 h T treatment (30 % decrease). Conclusions: Local estrogen formation within brain cells and tissue may be modulated by black cohosh, 17ß-estradiol, testosterone, and Tibolone's 3α-OH metabolite, respectively. The clinical implication of this finding has to be elucidated.

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Gene expression profiling reveals effects of Cimicifuga racemosa (L.) NUTT. (black cohosh) on the estrogen receptor positive human breast cancer cell line MCF-7

Cited by 56 publications

References 65 publications

The impact of testosterone, tibolone and black cohosh on purified mammary and placental 17β-hydroxysteroid dehydrogenase type 1

The impact of testosterone, tibolone and black cohosh on purified mammary and placental 17β-hydroxysteroid dehydrogenase type 1

Absence of positive effect of black cohosh (Cimicifuga racemosa) on fracture healing in osteopenic rodent model

Effects of black cohosh on estrogen biosynthesis in hippocampus of non-human primates ex vivo in vitro and in human neuroblastoma cells in vitro

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