Baicalein suppresses 17-β-estradiol-induced migration, adhesion and invasion of breast cancer cells via the G protein-coupled receptor 30 signaling pathway

Shang, Dandan; Li, Zheng; Zhu-xia, Zhu; Chen, Huamei; Zhao, Lujun; Wang, Xudong; Chen, Yan

doi:10.3892/or.2015.3786

Cited by 61 publications

(39 citation statements)

References 40 publications

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“…It has been well established that sustained exposure to E2 increases the risk of breast cancer (21), and inhibition of E2-mediated signaling has been suggested as a key strategy for the treatment of estrogen-dependent breast cancer (22,23). In the present study, it was demonstrated that treatment with E2 significantly enhanced the viability, migration and invasion of ERα-positive breast cancer cells.…”

Section: Discussionsupporting

confidence: 50%

MiR-203 inhibits estrogen-induced viability, migration and invasion of estrogen receptor α-positive breast cancer cells

Lin

Wang

Gao

et al. 2017

Experimental and Therapeutic Medicine

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Section: Discussionsupporting

confidence: 50%

MiR-203 inhibits estrogen-induced viability, migration and invasion of estrogen receptor α-positive breast cancer cells

Lin

Wang

Gao

et al. 2017

Experimental and Therapeutic Medicine

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“…These investigations propose that baicalein exerts anti-estrogenic activity and inhibitory effects on ERα transcriptional function. Recently, the authors of the current study demonstrated that baicalein suppresses E2-promoted migration and invasion in MCF-7 (GPR30/ERα-positive) and SK-BR-3 (GPR30-positive/ERα-negative) breast cancer cells (23). Furthermore, it was revealed that baicalein significantly inhibited E2-or G1-induced GPR30 signal activation and GPR30 target genes, cysteine-rich 61, and connective tissue growth factor upregulation (23).…”

Section: Discussionmentioning

confidence: 97%

“…Several studies have revealed that baicalein possesses antitumor activity in breast cancer and exhibits anti-estrogenic activity (20)(21)(22). In our previous study, it was demonstrated that baicalein is able to suppress E2 enhanced migration, adhesion and invasion of breast cancer cells and interferes with E2 or G-1 induced GPR30 signaling activation (23). However, whether this compound could inhibit E2 promoted MMP-9 upregulation and activation, as well as take effects via GPR30 remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Baicalein, unlike 4-hydroxytamoxifen but similar to G15, suppresses 17β-estradiol-induced cell invasion, and matrix metalloproteinase-9 expression and activation in MCF-7 human breast cancer cells

et al. 2017

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Abstract.Estrogen performs an important role in the growth and development of breast cancer. There are at least three major receptors, including estrogen receptor (ER)α and β, and G protein-coupled receptor 30 (GPR30), which mediate the actions of estrogen through using transcriptional and rapid non-genomic signaling pathways. Flavonoids have been considered candidates for chemopreventive agents in breast cancer. Baicalein, the primary flavonoid derived from the root of Scutellaria baicalensis Georgi, has been reported to exert an anti-estrogenic effect. In the present study, the effects of baicalein on 17β-estradiol (E2)-induced cell invasion, and matrix metalloproteinase-9 (MMP-9) expression and activation were investigated. Furthermore, its effects were compared with that of the active form of the ER modulator tamoxifen 4-hydroxytamoxifen (OHT) and the GPR30 antagonist G15 in ERα-and GPR30-positive MCF-7 breast cancer cells. The results demonstrated that OHT failed to prevent E2-induced cell invasion, upregulation and proteolytic activity of MMP-9. However, baicalein was able to significantly suppress these E2-induced effects. Furthermore, E2-stimulated invasion, and MMP-9 expression and activation were significantly attenuated following G15 treatment. In addition, baicalein significantly inhibited G-1, a specific GPR30 agonist, induced invasion, and reduced G-1 promoted expression and activity of MMP-9, consistent with effects of G15. The results of the present study suggest that baicalein is a therapeutic candidate for GPR30-positive breast cancer treatment, and besides ERα targeting the GPR30 receptor it may achieve additional therapeutic benefits in breast cancer. IntroductionIt is well known that the steroid hormone estrogen performs a role in the pathogenesis of breast cancer, and the majority of breast cancer types involve estrogen signaling pathways in cancer initiation, progression and metastasis (1). The majority of estrogen-associated biological actions are traditionally attributed to activate classic estrogen receptors (ERs), ERα and ERβ (2). Thus, endocrine therapies that interfere with ER functions are currently applied in patients with ER-positive breast cancer. Although targeted inhibition of ERα is a successful approach, numerous patients fail to respond (de novo resistance) or relapse despite an initial response (acquired resistance) to anti-estrogen therapy (3). The selective ER modulator tamoxifen, which antagonizes estrogen-induced genomic-nuclear ERα activity, is widely used in the treatment of ERα-positive breast cancer. It has significantly reduced the mortality risk among patients, however, not all patients achieve beneficial effects as disease recurrence occurs in ~25-30% of patients (4).The identification and characterization of the G protein-coupled receptor 30 (GPR30) represents an additional mechanism of estrogen effects, which mediate a wide range of estrogenic responses, leading to changes in gene expression and relevant biological responses (5). It has been revealed that GPR30...

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“…Previously, it has been shown that bacailein not only has a therapeutic effect on non-tumorous diseases, such as acute liver failure and acute myocardial ischemia (11,12), but it also exerts an inhibitory effect on tumor diseases, including colorectal, prostate, liver, lung, skin, stomach and ovarian cancer (13)(14)(15)(16)(17). It has been reported that baicalein has wide -ranging potential antitumor effects in terms of: i) Restraining cell proliferation, invasion and metastasis; ii) promoting cell apoptosis; iii) completely inhibiting the cell cycle; iv) preventing tumor angiogenesis; v) inducing tumor cell differentiation; and vi) removing reactive oxygen free radicals and preventing the tumorigenesis (7,18,19 (20). Consistently with the results of a study by Xu et al (21), the proliferative activity of the MDA-MB-231 cells was decreased in a concentration-and time-dependent manner.…”

Section: Chemical Structure and Physiological Function Of Baicaleinmentioning

confidence: 99%

“…Therefore, inhibiting tumor cell migration and invasion is also an important part in the treatment of tumor metastasis. A study by Shang et al (18) revealed that the results from the wound-healing assay indicated that the migration rate decreased to 17±2% in the MCF-7 cells, and 13±4% in the SK-BR-3 cells, following treatment with 15 µmol/l baicalein for 24 h; the Matrigel-coated Transwell chamber system was used to investigate the effects of baicalein on the invasion of MCF-7 and SK-BR-3 cells. Baicalein was evidently able to suppress cellular invasion in a concentration-and time-dependent manner.…”

Section: Breast Cancer Cell Migration and Inhibition Of Invasion Indumentioning

confidence: 99%

Latest research progress in the correlation between baicalein and breast cancer invasion and metastasis

Yan

Gao

et al. 2016

Molecular and Clinical Oncology

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Abstract. Breast cancer is one of the most commonly occurring female malignant tumors. According to the 2012 GLOBOCAN statistics, produced by the International Agency for Research On Cancer (ʻIARCʼ), nearly 1.7 million women were diagnosed with breast cancer, with 522,000 related deaths: An increase in the incidence of breast cancer and associated mortality by nearly 18% from 2008. Metastasis is the final step in breast cancer progression, and represents the most common cause of mortality in patients with breast cancer. Therefore, a search for low-toxicity, safe and effective anti-breast cancer drugs in the form of natural compounds has become an intense focus of research. Baicalein, a widely used Chinese herbal medicine, has extensive antitumor activity. The present review briefly describes the research that has been performed on the association between baicalein and breast cancer metastasis, and further illustrates the influence of baicalein on the underlying mechanisms of breast cancer metastasis, adding a novel theory basis for baicalein antitumor research. In conclusion, baicalein may represent a promising target for the prevention and therapy of breast cancer.

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Baicalein suppresses 17-β-estradiol-induced migration, adhesion and invasion of breast cancer cells via the G protein-coupled receptor 30 signaling pathway

Cited by 61 publications

References 40 publications

MiR-203 inhibits estrogen-induced viability, migration and invasion of estrogen receptor α-positive breast cancer cells

MiR-203 inhibits estrogen-induced viability, migration and invasion of estrogen receptor α-positive breast cancer cells

Baicalein, unlike 4-hydroxytamoxifen but similar to G15, suppresses 17β-estradiol-induced cell invasion, and matrix metalloproteinase-9 expression and activation in MCF-7 human breast cancer cells

Latest research progress in the correlation between baicalein and breast cancer invasion and metastasis

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