scholarly journals Antiestrogenic Activity of the Xi-Huang Formula for Breast Cancer by Targeting the Estrogen Receptor α

2018 ◽  
Vol 47 (6) ◽  
pp. 2199-2215 ◽  
Author(s):  
Jian Hao ◽  
Ziqi Jin ◽  
Hongxu Zhu ◽  
Xiaohui Liu ◽  
Yu Mao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Molecular Docking ◽  
Systems Biology ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Breast Cancer Treatment

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.

scholarly journals Development, Characterization and In Vitro Evaluation of Paclitaxel and Anastrozole Co-Loaded Liposome

Processes ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 1110
Author(s):  
Minh Thanh Vu ◽  
Dinh Tien Dung Nguyen ◽  
Ngoc Hoi Nguyen ◽  
Van Thu Le ◽  
The Nam Dao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Combination Therapy ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Breast Cancer Treatment ◽  
In Vitro Cytotoxicity ◽  
Cytotoxicity Studies ◽  
Combined Drugs

Paclitaxel (PTX) and anastrozole (ANA) have been frequently applied in breast cancer treatment. PTX is well-known for its anti-proliferative effect meanwhile ANA has just been discovered to act as an estrogen receptor α (ERα) ligand. The combination therapy of PTX and ANA is expected to improve treating efficiency, as ANA would act as a ligand binding with the ERα gene expressed in breast cancer cells and thereafter PTX would inhibit the division and cause death to those cancer cells. In this study, liposome-based nanocarriers (LP) were developed for co-encapsulation of PTX and ANA to improve the efficacy of the combined drugs in an Estrogen receptor-responsive breast cancer study. PTX-ANA co-loaded LP was prepared using thin lipid film hydration method and was characterized for morphology, size, zeta potential, drug encapsulation and in vitro drug release. In addition, cell proliferation (WST assay) and IN Cell Analyzer were used for in vitro cytotoxicity studies on a human breast cancer cell line (MCF-7). Results showed that the prepared LP and PTX-ANA-LP had spherical vesicles, with a mean particle size of 170.1 ± 13.5 nm and 189.0 ± 22.1 nm, respectively. Controlled and sustained releases were achieved at 72 h for both of the loaded drugs. The in vitro cytotoxicity study found that the combined drugs showed higher toxicity than each single drug separately. These results suggested a new approach to breast cancer treatment, consisting of the combination therapy of PTX and ANA in liposomes based on ER response.

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

2012 ◽  
Vol 83 (6) ◽  
pp. 723-732 ◽  
Author(s):  
Mitali Chattopadhyay ◽  
Ravinder Kodela ◽  
Niharika Nath ◽  
Arpine Barsegian ◽  
Daniel Boring ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Hydrogen Sulfide ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Estrogen Receptor Negative

scholarly journals Nitric Oxide-Releasing Aspirin Suppresses NF-κB Signaling in Estrogen Receptor Negative Breast Cancer Cells in Vitro and in Vivo

Molecules ◽  
2015 ◽  
Vol 20 (7) ◽  
pp. 12481-12499 ◽  
Author(s):  
Niharika Nath ◽  
Mitali Chattopadhyay ◽  
Deborah Rodes ◽  
Anna Nazarenko ◽  
Ravinder Kodela ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Nitric Oxide ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Nitric Oxide Releasing ◽  
Estrogen Receptor Negative

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

2019 ◽  
Vol 20 (4) ◽  
pp. 966 ◽  
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.

scholarly journals PLAC8 promotes adriamycin resistance via  blocking  autophagy in breast cancer

2020 ◽  
Author(s):  
yongxia chen ◽  
yunlu jia ◽  
misha mao ◽  
Yifeng Gu ◽  
Chenpu Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Breast Cancer Cell ◽  
Cell Response ◽  
Breast Cancer Cells ◽  
Breast Cancer Treatment ◽  
Autophagy Pathway ◽  
Mcf 7

Abstract Background Adriamycin (ADM) is currently one of the most effective chemotherapeutic agents in breast cancer treatment. However, growing resistance to ADM can lead to treatment failure and poor outcome. The underlying molecular mechanisms in ADM resistance in breast cancer remains unclear. PLAC8 is reported as a novel highly-conserved protein and functions as an oncogene or tumor suppressor in various tumors. Methods Here, we analyzed the expression profile of PLAC8 in breast cancer tissues and breast cancer cell lines, and explored the correlation of PLAC8 expression levels with patients’ outcomes and ADM response. One ADM resistant MCF-7 breast cancer cell (MCF-7/ADM) and its parental cell was used as in vitro models to identify the underlying mechanism of PLAC8 and ADM resistance. Breast cancer cells were transfected with PLAC8 knockdown and overexpression vectors, and MTT and colony formation assays were performed to test the cell response to ADM. Then, we tested the effect of PLAC8 on autophagy pathway by flow cytometry and immunofluorescence analysis, and the change of main autophagy-correlated factors expressions: LC3 and p62. Next, combining treatment of autophagy inhibitor/inducer and PLAC8 downregulation/upregulation revealed the participation of PLAC8 in autophagy pathway to synergistically regulate ADM resistance in breast cancer. Results Here, higher PLAC8 expression was correlated with poorer outcome and aggressive phenotype in breast cancer, and breast cancer patients with higher PLAC8 expression showed potential ADM resistance. PLAC8 expression level was also significantly elevated in ADM resistant MCF-7 breast cancer cells (MCF-7/ADM), compared to parental MCF-7 cells. In vitro experiments further confirmed that PLAC8 inhibition by siRNA or enforced overexpression by infecting pcDNA3.1(C)-PLAC8 plasmid correspondingly decreased or increased the ADM resistance. Subsequently, we demonstrated that ectopic PLAC8 expression in MCF-7/ADM cell blocked the accumulation of the autophagy-associated protein LC3II, and resulted in cellular accumulation of p62. Rapamycin-triggered autophagy significantly increased cell response to ADM, while the autophagy inhibitor 3-MA enhanced ADM resistance. Actually, 3-MA and PLAC8 could synergistically enhance ADM resistance via blocking the autophagy process. Additionally, the downregulation of p62 by siRNA attenuated the activation of autophagy and PLAC8 expression in breast cancer cells. Conclusion Our findings suggest that PLAC8, through participation of p62, inhibits autophagy and consequently results in ADM resistance in breast cancer. PLAC8/p62/autophagy pathway may act as novel therapeutic targets in breast cancer treatment and has potential clinical application in overcoming ADM resistance.

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

2003 ◽  
Vol 73 (1) ◽  
pp. 19-23 ◽  
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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