Hydrogen sulfide-releasing aspirin suppresses NF-κB signaling in estrogen receptor negative breast cancer cells in vitro and in vivo

Background/Aims: The Xi-Huang (XH) formula has been used for breast cancer treatment in traditional Chinese medicine (TCM) since 1740. In this study, we show that, XH extract could suppress the growth of breast cancer cells in vitro and in vivo, and that it preferentially inhibits cell growth of estrogen receptor positive (ER+) breast cancer cells. Presently, little is known about the potential mechanism of XH and our studies aim to elucidate its mechanism in breast cancer treatment. Methods: Network-based systems biology and molecular docking analyses were performed to predict explicit targets of XH and active ingredients in XH. The effects of XH on cell viability, cell cycle, apoptosis in different breast cancer cell lines were analyzed in vitro. A model of transplanted tumors on nude mice was used to study the anticancer effect in vivo. Various techniques, including western blotting, reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence, co-immunoprecipitation and immunohistochemical were utilized to assess the expression of targets of XH in vitro and in vivo. RNA sequencing (RNA-seq) was performed to study the gene targets of XH. Furthermore, we analyzed of protein-ligand binding reactions by isothermal titration calorimetry (ITC). Results: Using network-based systems biology and molecular docking analyses, we predicted that the major targets of XH were ERα and HSP90. Moreover, we found that, XH mediated its anti-cancer effects by promoting the disassociation of ERα and HSP90, resulting in the degradation of ERα and blockade of transport of ERα to the nucleus. XH also caused the dissociation of ERα and other oncoproteins via binding to HSP90. Some of the active ingredients in XH share a common cyclopentane hydrogen skeleton and were predicted to target ERα based on the structural similarity. Conclusions: XH, which has been used since 1740, has antiestrogenic effects in breast cancer via the targeting of ERα.

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BCAS2 Enhances Carcinogenic Effects of Estrogen Receptor Alpha in Breast Cancer Cells

International Journal of Molecular Sciences ◽

10.3390/ijms20040966 ◽

2019 ◽

Vol 20 (4) ◽

pp. 966 ◽

Cited By ~ 2

Author(s):

Ángel Salmerón-Hernández ◽

María Noriega-Reyes ◽

Albert Jordan ◽

Noemi Baranda-Avila ◽

Elizabeth Langley

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Cancer Cells ◽

Transcriptional Activation ◽

Cancer Biology ◽

Breast Cancer Cells ◽

Estrogen Receptor Alpha ◽

Receptor Alpha

Estrogen receptor alpha (ERα) has an established role in breast cancer biology. Transcriptional activation by ERα is a multistep process modulated by coactivator and corepressor proteins. Breast Cancer Amplified Sequence 2 (BCAS2), is a poorly studied ERα coactivator. In this work, we characterize some of the mechanisms through which this protein increases ERα activity and how this promotes carcinogenic processes in breast cancer cells. Using protein-protein interaction and luciferase assays we show that BCAS2 interacts with ERα both in vitro and in vivo and upregulates transcriptional activation of ERα directly through its N-terminal region (AF-1) and indirectly through its C-terminal (AF-2) region, acting in concert with AF-2 interacting coactivators. Elevated expression of BCAS2 positively affects proliferation, clonogenicity and migration of breast cancer cells and directly activates ERα regulated genes which have been shown to play a role in tumor growth and progression. Finally, we used signal transduction pathway inhibitors to elucidate how BCAS2 is regulated in these cells and observed that BCAS2 is preferentially regulated by the PI3K/AKT signaling pathway. BCAS2 is an AF-1 coactivator of ERα whose overexpression promotes carcinogenic processes, suggesting an important role in the development of estrogen-receptor positive breast cancer.

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Ergosterol (Major Sterol of Baker’s and Brewer’s Yeast Extracts) Inhibits the Growth of Human Breast Cancer Cells in vitro and the Potential Role of its Oxidation Products

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.73.1.19 ◽

2003 ◽

Vol 73 (1) ◽

pp. 19-23 ◽

Cited By ~ 29

Author(s):

M. T. Ravi Subbiah ◽

W. Abplanalp

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Oxidation Products ◽

Brewer’S Yeast ◽

Brewer's Yeast ◽

Mcf 7

The derivation of chemopreventive agents from dietary sources has been the subject of considerable attention in recent years. Yeast extracts have been used as nutritional supplements for a number of years. In this communication we show that ergosterol (a 28-carbon sterol found in baker’s and brewer’s yeast) can prevent growth of breast cancer cells in vitro in the presence of estradiol-17beta. Estrogen receptor (+) MCF-7 cells appear to be more sensitive to ergosterol than estrogen receptor (–) MDA-231 cells. However, MDA-231 cells were more sensitive to ergosterol in terms of apoptotic effects than MCF-7 cells, indicating that other mechanisms (antiestrogenic activity) may also be operative in estrogen receptor (+) cells. Compared to freshly prepared ergosterol, stored preparations were more potent in inhibiting growth of cancer cells, indicating that oxidation product(s) of ergosterol may be responsible for the noted effects. Further studies on in vivo effects of ergosterol and lipid extracts of yeast in animal models are warranted to determine their potential for use as supplements in humans.

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