Genistein: Its Role in Breast Cancer Growth and Metastasis

Mukund, Vidya

doi:10.2174/1389200221666200120121919

Cited by 26 publications

(11 citation statements)

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“…The EGFR/Akt/NFκB pathway modulation play a role in cell differentiation [58], which leads to cancer cell death. With genistein, the activity of Akt is suppressed, promoting the deactivation of downstream signaling pathways, including NF-κB [2,59]. This was demonstrated by the electrophoretic mobility shift assay in MDA-MB-231 cells, along with inhibition in the activation of Akt by preventing EGF signal triggering [59].…”

Section: Cell Cycle Arrest and Anti-proliferative Mechanismmentioning

confidence: 97%

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Genistein: A Potent Anti-Breast Cancer Agent

Bhat

Prasad

Shivamallu

et al. 2021

CIMB

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Genistein is an isoflavonoid present in high quantities in soybeans. Possessing a wide range of bioactives, it is being studied extensively for its tumoricidal effects. Investigations into mechanisms of the anti-cancer activity have revealed many pathways including induction of cell proliferation, suppression of tyrosine kinases, regulation of Hedgehog-Gli1 signaling, modulation of epigenetic activities, seizing of cell cycle and Akt and MEK signaling pathways, among others via which the cancer cell proliferation can be controlled. Notwithstanding, the observed activities have been time- and dose-dependent. In addition, genistein has also shown varying results in women depending on the physiological parameters, such as the early or post-menopausal states.

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Section: Cell Cycle Arrest and Anti-proliferative Mechanismmentioning

confidence: 97%

“…Several in vitro and in vivo studies have attempted to understand and gain a better insight into the mechanisms underlying the biomedical properties of genistein [2][3][4]. The isoflavonoid has been analyzed and previously reviewed for its neoplastic potentials.…”

Section: Introductionmentioning

confidence: 99%

Genistein: A Potent Anti-Breast Cancer Agent

Bhat

Prasad

Shivamallu

et al. 2021

CIMB

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“…Several studies have been performed to better understand the mechanisms of its beneficial effects in different diseases. In vivo and in vitro analyses indicated that genistein can modulate numerous signaling cascades in several types of cancer cells, that results in decreased cell viability, and promotion of cell death [ 5 ]. Figure 1 illustrates the molecular interactions of genistein in different cellular pathways.…”

Section: Introductionmentioning

confidence: 99%

“…Genistein directly suppresses the activity of Akt and therefore this substance promotes the inactivation of its downstream signaling pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) [ 5 – 7 ]. The electrophoretic mobility shift assay further demonstrated that treatment with genistein directly inactivates NF-κB in MDA-MB-231 cells [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Genistein as a regulator of signaling pathways and microRNAs in different types of cancers

et al. 2021

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Cancers are complex diseases orchestrated by a plethora of extrinsic and intrinsic factors. Research spanning over several decades has provided better understanding of complex molecular interactions responsible for the multifaceted nature of cancer. Recent advances in the field of next generation sequencing and functional genomics have brought us closer towards unravelling the complexities of tumor microenvironment (tumor heterogeneity) and deregulated signaling cascades responsible for proliferation and survival of tumor cells. Phytochemicals have begun to emerge as potent beneficial substances aimed to target deregulated signaling pathways. Isoflavonoid genistein is an essential phytochemical involved in regulation of key biological processes including those in different types of cancer. Emerging preclinical evidence have shown its anti-cancer, anti-inflammatory and anti-oxidant properties. Testing of this substance is in various phases of clinical trials. Comprehensive preclinical and clinical trials data is providing insight on genistein as a modulator of various signaling pathways both at transcription and translation levels. In this review we have explained the mechanistic regulation of several key cellular pathways by genistein. We have also addressed in detail various microRNAs regulated by genistein in different types of cancer. Moreover, application of nano-formulations to increase the efficiency of genistein is also discussed. Understanding the pleiotropic potential of genistein to regulate key cellular pathways and development of efficient drug delivery system will bring us a step towards designing better chemotherapeutics.

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“…GE acts as a potent chemopreventive and therapeutic agent against various types of cancers including breast, prostate, and lung cancer [9,10]. The mechanisms by which GE elicits its anti-carcinogenic properties involve inhibition of cellular proliferation, angiogenesis, and metastasis as well as induction of apoptosis, differentiation, and cell cycle arrest at the G2-M phase [11][12][13]. Specifically, it is known to inhibit breast carcinogenesis by regulation of several signaling pathways such as downregulation of VEGF, HIF-1α, MMPs, fibronectin, JNK, ERK/PI3K/AKT axis and upregulation of p21 [11,13].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Effects of Dietary Soybean Genistein on Triple-Negative Breast Cancer via Regulation of Epigenetic Mechanisms

et al. 2021

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Consumption of dietary natural components such as genistein (GE) found in soy-rich sources is strongly associated with a lower risk of breast cancer. However, bioactive dietary component-based therapeutic strategies are largely understudied in breast cancer treatment. Our investigation sought to elucidate the potential mechanisms linking bioactive dietary GE to its breast cancer chemotherapeutic potential in a special subtype of aggressive breast cancer—triple-negative breast cancer (TNBC)—by utilizing two preclinical patient-derived xenograft (PDX) orthotopic mouse models: BCM-3204 and TM00091. Our study revealed that administration of GE resulted in a delay of tumor growth in both PDX models. With transcriptomics analyses in TNBC tumors isolated from BCM-3204 PDXs, we found that dietary soybean GE significantly influenced multiple tumor-regulated gene expressions. Further validation assessment of six candidate differentially expressed genes (DEGs)—Cd74, Lpl, Ifi44, Fzd9, Sat1 and Wwc1—demonstrated a similar trend at gene transcriptional and protein levels as observed in RNA-sequencing results. Mechanistically, GE treatment-induced Cd74 downregulation regulated the NF-κB/Bcl-xL/TAp63 signal pathway, which may contribute to soybean GE-mediated therapeutic effects on TNBC tumors. Additionally, our findings revealed that GE can modify expression levels of key epigenetic-associated genes such as DNA methyltransferases (Dnmt3b), ten-eleven translocation (Tet3) methylcytosine dioxygenases and histone deacetyltransferase (Hdac2), and their enzymatic activities as well as genomic DNA methylation and histone methylation (H3K9) levels. Collectively, our investigation shows high significance for potential development of a novel therapeutic approach by using bioactive soybean GE for TNBC patients who have few treatment options.

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Genistein: Its Role in Breast Cancer Growth and Metastasis

Cited by 26 publications

References 0 publications

Genistein: A Potent Anti-Breast Cancer Agent

Genistein: A Potent Anti-Breast Cancer Agent

Genistein as a regulator of signaling pathways and microRNAs in different types of cancers

Therapeutic Effects of Dietary Soybean Genistein on Triple-Negative Breast Cancer via Regulation of Epigenetic Mechanisms

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