Anticancer effect of genistein on BG-1 ovarian cancer growth induced by 17 β-estradiol or bisphenol A via the suppression of the crosstalk between estrogen receptor alpha and insulin-like growth factor-1 receptor signaling pathways

Hwang, Kyung‐A; Park, Min-Ah; Kang, Nam‐Hee; Yi, Bo‐Rim; Hyun, Sang‐Hwan; Jeung, Eui‐Bae; Choi, Kyung‐Chul

doi:10.1016/j.taap.2013.07.027

Cited by 70 publications

(34 citation statements)

References 44 publications

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“…GEN also targets AKT and p21 WAF1/CIP1 in BRCA1-mutant human breast cancer cell lines [527], GEN induced AKT-mediated enhanced apoptosis/downregulation of AKT has also been reported in combination with compounds like arsenic trioxide in human hepatocellular carcinoma [528], gefitinib in NSCLS [529], gemcitabine in human osteosarcoma [522, 530], cisplatin in cervical cancer cells [531], cetuximab in oral squamous cell carcinoma [532], photoactivated hypericin in breast cancer cells [533] and indole-3-carbinol in human colon cancer HT-29 cells [534]. GEN also inhibits the carcinogenic effect of 17 beta estradiol or bisphenol-A via ER/IGF-1/AKT pathway in BG-1 ovarian cancer cells [535] and also downregulates FOXO3 activity in colon cancer cells [524]. It also modulates MAPKs/AKT in cervical cancer cells.…”

Section: Low Toxicity Approachesmentioning

confidence: 99%

A multi-targeted approach to suppress tumor-promoting inflammation

Samadi

Bilsland

Georgakilas

et al. 2015

Seminars in Cancer Biology

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Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-kappaB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes.

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Section: Low Toxicity Approachesmentioning

confidence: 99%

A multi-targeted approach to suppress tumor-promoting inflammation

Samadi

Bilsland

Georgakilas

et al. 2015

Seminars in Cancer Biology

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“…Meanwhile, accumulating evidence proves that some phytoestrogens exhibit antiestrogenic activity via ER-mediated signaling pathway [16,17,18]. For example, Nakamura et al reported that genistein, an isoflavone found in soy, inhibited proliferation and decreased invasive potential of human osteosarcoma cell line LM8, indicating the role of phytoestrogens in the prevention and treatment of osteosarcomas [19].…”

Section: Discussionmentioning

confidence: 99%

The Proapoptotic Effect of Formononetin in Human Osteosarcoma Cells: Involvement of Inactivation of ERK and Akt Pathways

Liu¹,

He²,

Chen³

et al. 2014

Cell Physiol Biochem

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Background: Previous studies have shown that some phytoestrogens inhibits proliferation and induces apoptosis in estrogen-dependent cancers via estrogen receptor (ER)-mediated signaling pathway. In view of the expression of ER in human osteosarcoma cells, the purpose of this study is to investigate whether formononetin and calycosin, two of the major isoflavones in Radix astragali, could also elicit anti-tumor activity against osteosarcoma, along with the underlying mechanism. Methods: Human osteosarcoma cells U2OS were respectively treated with various concentrations of formononetin or calycosin. Cell proliferation was determined by MTT assay, while apoptosis by flow cytometry. Next, the expression levels of apoptosis-related genes ERK, Akt, Bcl-2, Bax and caspase-3 were quantified by real-time PCR and Western blotting. Results: Formononetin exhibited higher anti-proliferative activities toward human osteosarcoma cells U2OS, when compared with calycosin. Therefore, U2OS cells were then respectively treated with various concentrations of formononetin, in order to elucidate the isoflavones-related signaling pathway. It was found that formononetin dose-dependently triggered apoptosis of U2OS cells in vitro. Furthermore, treatment of formononetin led to significant inactivation of ERK and Akt, followed by downregulation of Bcl-2, upregulation of Bax and finally increased expression of caspase-3. Conclusion: Formononetin is more effective than calycosin at promoting cell death of U2OS cells by induction of apoptosis, which is mediated by inactivation of ERK and Akt signaling pathways. Thus isoflavones, especially formononetin, may be useful as anti-cancer drugs for osteosarcoma through their apoptosis-inducing effects.

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“…One group shows that the phytoestrogens resveratrol and genistein inhibit estrogen-induced proliferation of ERα-positive BG-1 cancer cells by suppressing ERα and IGF-IR gene expression and ERα, phospho-IRS1, phospho-AKT and Cyclin D1 protein expression [29, 30]. The authors speculate that resveratrol acts by inhibiting ligand binding of ERα and by preventing ligand bound ERα from interacting with phospho-IRS1 [30].…”

Section: Estrogen Signaling Crosstalkmentioning

confidence: 99%

“…Moreover, epidemiological studies, which reveal that long-term use of estrogen-only hormone replacement therapy increases a woman's risk of ovarian cancer, support the hypothesis that estrogen-signaling contributes to the etiology of the disease [22-25]. In addition, experimental studies demonstrate the growth promoting effects of estrogen on ovarian tumors in mice [26-28] and in human ovarian cancer cell lines [29-31]. Thus, while anti-estrogen therapies alone may be ineffective, they should not be ruled out as part of future combinatorial therapeutic approaches to better treat ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

“…In this manner, the relative levels of ER corepressors and coactivators can also affect tumor progression and response to hormone therapy [32, 49]. The differential functions of the various ERs play an important role in ovarian cancer as well; ERα [29, 50-53] and GPER1 [52, 54-56] are primarily thought to be protumorigenic, whereas studies report ERβ to be primarily anti-proliferative [57-60]. …”

Section: Introductionmentioning

confidence: 99%

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Estrogen signaling crosstalk: Implications for endocrine resistance in ovarian cancer

Ribeiro

Freiman

2014

The Journal of Steroid Biochemistry and Molecular Biology

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Resistance to anti-estrogen therapies is a prominent challenge in the treatment of ovarian cancer. Tumors develop endocrine resistance by acquiring adaptations that help them rely on alternative oncogenic signaling cascades, which crosstalk with estrogen signaling pathways. An understanding of estrogen signaling crosstalk with these growth promoting cascades is essential in order to maximize efficacy of anti-estrogen treatments in ovarian cancer. Herein, we provide an overview of estrogen signaling in ovarian cancer and discuss the major challenges associated with anti-estrogen therapies. We also review what is currently known about how genomic and non-genomic estrogen signaling pathways crosstalk with several major oncogenic signaling cascades. The insights provided here illustrate existing strategies for targeting endocrine resistant ovarian tumors and may help identify new strategies to improve the treatment of this disease.

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Anticancer effect of genistein on BG-1 ovarian cancer growth induced by 17 β-estradiol or bisphenol A via the suppression of the crosstalk between estrogen receptor alpha and insulin-like growth factor-1 receptor signaling pathways

Cited by 70 publications

References 44 publications

A multi-targeted approach to suppress tumor-promoting inflammation

A multi-targeted approach to suppress tumor-promoting inflammation

The Proapoptotic Effect of Formononetin in Human Osteosarcoma Cells: Involvement of Inactivation of ERK and Akt Pathways

Estrogen signaling crosstalk: Implications for endocrine resistance in ovarian cancer

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