Huaier polysaccharide inhibits the stem-like characteristics of ERα-36high triple negative breast cancer cells via inactivation of the ERα-36 signaling pathway

Hu, Baoquan; Yan, Wei; Wang, Minghao; Cui, Xiang; Ying, Hanjie; Chen, Qingqiu; Zhang, Yi; Qi, Xiaowei; Jiang, Jun

doi:10.7150/ijbs.27360

Cited by 27 publications

(18 citation statements)

References 41 publications

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“…According to the HPLC (high performance liquid chromatography) and SDS-PAGE (polyacrylamide gel electrophoresis) analysis, the most effective ingredient of Huaier is identified as proteoglycan, which includes 41.53% polysaccharides, 12.93% amino acids and 8.72% water (1). Polysaccharide was identified as a possible key ingredient in Huaier (2–4). Previous studies showed that Huaier exerted therapeutic effects on psoriasis (5), inflammation (6), and tuberous sclerosis (7).…”

Section: Introductionmentioning

confidence: 99%

Huaier Suppresses Breast Cancer Progression via linc00339/miR-4656/CSNK2B Signaling Pathway

Wang

et al. 2019

Front. Oncol.

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Huaier, as known as Trametes robiniophila Murr, is a traditional Chinese medicine. Various studies have demonstrated that Huaier could inhibit cancer progression and improve the prognosis of patients. In the present study, we comprehensively screened the expression profiles of lncRNAs, miRNAs, and mRNAs in Huaier-treated breast cancer cells. Using bioinformatic analysis, hub genes were identified and functionally annotated. Weighted gene coexpression network analysis was applied to construct the molecular network influenced by Huaier. Linc00339 was then found to play a critical role in Huaier-mediated cancer suppression. To validate the effects of linc00339 and identify the downstream targets, we performed in vitro and in vivo experiments. Finally, we identified that Huaier could inhibit the proliferation of breast cancer cells through modulating linc00339/miR-4656/CSNK2B signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Huaier Suppresses Breast Cancer Progression via linc00339/miR-4656/CSNK2B Signaling Pathway

Wang

et al. 2019

Front. Oncol.

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“…The effect of estrogen in breast cancer is no longer rely on the expression of ER (predominantly ERα). The role of other subtypes of estrogen receptors, such as ERβ 29,46,47 and ERα36, 48,49 as well as other receptors or effectors related to ER signaling, such as GPER and ERR family, are raising concern in TNBC. However, the cross-talk among different ER subtypes or effectors related to ER signaling could be extremely complicated.…”

Section: Discussionmentioning

confidence: 99%

Estrogen-Related Receptor α (ERRα) and G Protein-Coupled Estrogen Receptor (GPER) Synergistically Indicate Poor Prognosis in Patients with Triple-Negative Breast Cancer

Zhou

et al. 2020

OTT

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The present study aims to demonstrate the correlation between estrogen-related receptor α (ERRα) and G protein-coupled estrogen receptor (GPER) expression and its predictive role in the prognosis of patients with triple-negative breast cancer (TNBC). Methods: A retrospective review of 199 cases of TNBC was conducted to assess the GPER and ERRα expression, and its clinicopathologic and prognostic implications. Subsequently, the effects of ERRα and GPER on cell viability, migration, and invasion induced by estrogen were also investigated in vitro. Results: Compared to TNBCs with ERRα low expression, ERRα-high patients exhibited higher nuclear grade, more frequent lymph nodal metastasis, a higher rate of local recurrence, and distant metastasis. Survival analyses revealed that ERRα-high patients had decreased overall survival (OS), local recurrence-free survival (LRFS), and distant diseasefree survival (DDFS) than ERRα-low patients. The GPER expression level positively correlated with ERRα (R=0.167, P=0.18), and TNBCs with ERRα-low/GPER-low demonstrated the best survival outcomes among groups. In vitro, E2 significantly enhanced cell viability, migration, and invasion in BT-549 and MDA-MB-231 cell lines, which was associated with the increased expression of ERRα. Moreover, the overexpression of ERRα induced by estrogen and G1 (GPER agonist) was reversed by knocking down of GPER and blocking the MAPK signaling with PD98059 in both cell lines. Conclusion: Our findings suggest that ERRα and GPER synergistically predict unfavorable prognosis in TNBCs. Mechanically, GPER mediates the upregulation expression of ERRα induced by estrogen and promotes cell viability, migration, and invasion.

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“…14 As pointed out in recent explorations, Huaier extract could play an anti-tumor role in a variety of malignant tumors, such as gastric cancer, lung cancer, osteosarcoma and breast cancer. [15][16][17][18] Meanwhile, Huaier could also strengthen the organic immunity by up-regulating the activity of natural killer cells and T cell subsets. 19 Although the role of Huaier in some common malignancies has been reported in scatter studies, the potential effect and exact mechanism in human CCA are still not fully revealed.…”

Section: Introductionmentioning

confidence: 99%

Huaier Restrains Cholangiocarcinoma Progression in vitro and in vivo Through Modulating lncRNA TP73-AS1 and Inducing Oxidative Stress

Zheng

Huang

et al. 2020

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Purpose: Huaier, the fruiting body of Trametes robiniophila Murr, is a kind of traditional Chinese medicine. Recently, many studies have confirmed that Huaier has antitumor effects on various malignancies. Moreover, studies have demonstrated that long noncoding RNAs play an important regulatory role in the occurrence and progression of malignancies. Our present study was to explore whether Huaier has a potential antitumor effect in cholangiocarcinoma and reveal the relationship between lncRNAs and Huaier-induced tumor inhibition. Methods: Microarray assay was performed to identify the candidate lncRNAs regulated by Huaier. Quantitative real-time PCR was applied to assess the effect of Huaier on TP73-AS1 expression. The effect of Huaier on the cell viability, proliferation, migration and invasion was evaluated by CCK-8, colony formation, wound healing and Transwell assays, respectively. The ratio of cell apoptosis was determined using AO/EB, Hoechst 33342 and flow cytometry. The effect of Huaier on oxidative stress was revealed using DCFH-DA, mito-SOX, JC-1 probes and Western blotting. In addition, the effect of Huaier on tumor growth and metastasis was explored using subcutaneous tumor model and lung metastatic tumor model in nude mice. Results: In vitro, Huaier inhibited the proliferation, migration and invasion of cholangiocarcinoma cells by down-regulating TP73-AS1 and induced apoptosis through mitochondrial apoptotic pathway. In vivo, Huaier suppressed the growth and metastasis of cholangiocarcinoma by modulating the expression of proliferation and EMT-associated proteins. Conclusion: Huaier could inhibit cell proliferation, invasion and metastasis by modulating the expression of TP73-AS1, meanwhile promote apoptosis of CCA cells through disturbing mitochondrial function, inducing oxidative stress and activating caspases in vitro. In addition, Huaier could suppress tumor growth and metastasis by regulating the expression of proliferation and EMT-related proteins. In the meantime, Huaier prolonged the survival of nude mice in lung metastatic model with acceptable drug safety.

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Huaier polysaccharide inhibits the stem-like characteristics of ERα-36^high triple negative breast cancer cells via inactivation of the ERα-36 signaling pathway

Cited by 27 publications

References 41 publications

Huaier Suppresses Breast Cancer Progression via linc00339/miR-4656/CSNK2B Signaling Pathway

Huaier Suppresses Breast Cancer Progression via linc00339/miR-4656/CSNK2B Signaling Pathway

<p>Estrogen-Related Receptor α (ERRα) and G Protein-Coupled Estrogen Receptor (GPER) Synergistically Indicate Poor Prognosis in Patients with Triple-Negative Breast Cancer</p>

<p>Huaier Restrains Cholangiocarcinoma Progression in vitro and in vivo Through Modulating lncRNA TP73-AS1 and Inducing Oxidative Stress</p>

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