Genistein downregulates onco-miR-1260b and inhibits Wnt-signalling in renal cancer cells

Hirata, Hiroshi; Ueno, Koji; Nakajima, Koichi; Tabatabai, Z. Laura; Hinoda, Yuji; Ishii, Nobuhisa; Dahiya, Rajvir

doi:10.1038/bjc.2013.173

Cited by 128 publications

(104 citation statements)

References 26 publications

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“…Collectively, the antitumor effects of gemcitabine in HuCCT-1 cells might be related to the reduction of these miRNAs. miR-1260b, in particular, has been recognized as an onco-miRNA, because the antitumor effect molecule genistein downregulates onco-miR-1260b and inhibits the Wnt-β-catenin signaling pathway, which is involved in cell growth (37). The Wnt-β-catenin signaling pathway is activated during CCC tumorigenesis (45).…”

Section: Discussionmentioning

confidence: 99%

Mechanism of gemcitabine-induced suppression of human cholangiocellular carcinoma cell growth

Toyota

Iwama

Kato

et al. 2015

International Journal of Oncology

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Abstract. Although gemcitabine (2',2'-difluorocytidine monohydrochloride) is a common anticancer agent of cholangiocellular carcinoma (CCC), its growth inhibitory effects and gemcitabine resistance in CCC cells are poorly understood. Our aims were to uncover the mechanism underlying the antitumor effect of gemcitabine and to analyze the mechanism regulating in vitro CCC cell gemcitabine resistance. In addition, we sought to identify miRNAs associated with the antitumor effects of gemcitabine in CCCs. Using a cell proliferation assay and flow cytometry, we examined the ability of gemcitabine to inhibit cell proliferation in three types of human CCC cell lines (HuCCT-1, Huh28, TKKK). We also employed western blotting to investigate the effects of gemcitabine on cell cycle-related molecules in CCC cells. In addition, we used array chips to assess gemcitabine-mediated changes in angiogenic molecules and activated tyrosine kinase receptors in CCC cells. We used miRNA array chips to comprehensively analyze gemcitabine-induced miRNAs and examined clusters of differentially expressed miRNAs in cells with and without gemcitabine treatment. Gemcitabine inhibited cell proliferation in a dose-and time-dependent manner in HuCCT-1 cells, whereas cell proliferation was unchanged in Huh28 and TKKK cells. Gemcitabine inhibited cell cycle progression in HuCCT-1 cells from G0/G1 to S phase, resulting in G1 cell cycle arrest due to the reduction of cyclin D1 expression. In addition, gemcitabine upregulated the angiogenic molecules IL-6, IL-8, ENA-78 and MCP-1. In TKKK cells, by contrast, gemcitabine did not arrest the cell cycle or modify angiogenic molecules. Furthermore, in gemcitabine-sensitive HuCCT-1 cells, gemcitabine markedly altered miRNA expression. The miRNAs and angiogenic molecules altered by gemcitabine contribute to the inhibition of tumor growth in vitro.

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Section: Discussionmentioning

confidence: 99%

Mechanism of gemcitabine-induced suppression of human cholangiocellular carcinoma cell growth

Toyota

Iwama

Kato

et al. 2015

International Journal of Oncology

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“…A study showed inhibition by the phenol of β-catenin -mediated WNT signaling through gene expression by demethylating its silenced promoter in colon cancer cell lines (Zhang & Chen, 2011). A similar study with renal cancer cells also showed inhibition of Wnt-signaling, thus effecting the proliferation and renewal of cancer stem cells (Hirata, Ueno, Nakajima et al, 2013). Data showed genistein, a natural chemo-preventive agent, inhibited cell growth, clonogenicity, cell migration and invasion, epithelial-mesemchymal transition, cancer stem cell phenotype, and formation of pancreatospheres in pancreatic cancer cells (Bao, Wang, Ali et al, 2011;Bao, Wang, Ali et al, 2011).…”

Section: Figure 2 Genisteinmentioning

confidence: 91%

Unifying Mechanism for Nutrients as Anticancer Agents: Electron Transfer, Reactive Oxygen Species and Oxidative Stress

Kovacic¹,

Somanathan²

2017

GJHS

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A recent article deals with various nutrients in relation to bactericidal action. The present article focuses on a unifying mode of action for the nutrients, namely, resveratrol, epigallocatechin, polyene-ß-carotene, polyene lycopene, piperine, curcumin, genistein, luteolin, sulforaphane and pomegranate extract. The mechanism is based on electron transfer, reactive oxygen species and oxidative stress, which comprises an extension of earlier reports involving agents. Most of the compounds are precursors of electron transfer quinones, whereas others fit into the polyene category. The nutrients are better known as antioxidants. The dichotomy is addressed.

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“…Treatment of ovarian and pancreatic cancer cells with genistein causes inhibition of cell growth and migration through suppression of miR-27a [79,80] . Furthermore, genistein upregulates the tumor suppressor miR-574-3p in prostate cancer cells [81] , and exerts its antitumor effect in prostate cancer via downregulation of miR-1260b [82] . Genistein treatment downregulates oncogenic miR-1260b and results in inhibition of Wnt-signaling in renal cancer cells [82] .…”

Section: Genisteinmentioning

confidence: 99%

“…Furthermore, genistein upregulates the tumor suppressor miR-574-3p in prostate cancer cells [81] , and exerts its antitumor effect in prostate cancer via downregulation of miR-1260b [82] . Genistein treatment downregulates oncogenic miR-1260b and results in inhibition of Wnt-signaling in renal cancer cells [82] . Additionally, miR-223 expression is downregulated in pancreatic cancer cells after genistein treatment that correlated with cell growth inhibition and induction of apoptosis [83] .…”

Section: Genisteinmentioning

confidence: 99%

Modulation of miRNAs by Natural Agents: Nature’s way of dealing with cancer

Masika

Zhao

Hescheler

et al. 2015

RNA Dis

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Accumulating lines of evidence have revealed that microRNAs (miRNAs) play critical roles in many biological processes, such as carcinogenesis, angiogenesis, programmed cell death, cell proliferation, invasion, migration, and differentiation. They act either as tumor suppressors or oncogenes, and alteration in their expression patterns has been linked to onset, progression and chemoresistance of various cancers. Moreover, miRNAs are also crucial for the regulation of cancer stem cells (CSCs) self-renewal and proliferation as well as control of Epithelial-to-Mesenchymal Transition (EMT) of cancer cells. Therefore, exploitation of miRNAs as targets for cancer prevention and therapy could be a promising approach. Several experimental and epidemiologic studies have shown that dietary intake of natural agents such as baicalin, ginsenoside, curcumin, resveratrol, genistein, epigallocatechin-3-gallate (EGCG), indole-3-carbinol, 3,3΄-diindolylmethane (DIM) including antioxidants among others is inversely associated with the risk for cancer, demonstrating the inhibitory effects of natural agents on carcinogenesis. Additionally, the anticancer agents from natural agents have been found to inhibit the development and progression of cancer through the regulation of various cancer processes such as apoptosis, cell cycle regulation, differentiation, inflammation, angiogenesis, and metastasis. Importantly, natural agents could significantly impact the expression of tumor-suppressor and oncogenic miRNAs, regulate cellular signaling networks, inhibit cancer cell growth and cancer stem cell self-renewal. This is important for the normalization of altered cellular signaling mechanisms in cancer cells. This postulates a much broader use of natural agents in the prevention and/or treatment of various cancers in combination with conventional chemotherapeutics. However, more in vitro mechanistic experiments, in vivo animal studies, and clinical trials are warranted to realize the true value of natural agents in the prevention and/or treatment of cancer. Herein, we provide an overview of natural agents' modulation of miRNA expression as well as highlight the significance of these observations as potential new strategies in cancer therapies. This review will help us to understand how miRNAs are regulated by natural agents and also help in the development of effective and secure natural agents for therapeutic purposes.

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Genistein downregulates onco-miR-1260b and inhibits Wnt-signalling in renal cancer cells

Cited by 128 publications

References 26 publications

Mechanism of gemcitabine-induced suppression of human cholangiocellular carcinoma cell growth

Mechanism of gemcitabine-induced suppression of human cholangiocellular carcinoma cell growth

Unifying Mechanism for Nutrients as Anticancer Agents: Electron Transfer, Reactive Oxygen Species and Oxidative Stress

Modulation of miRNAs by Natural Agents: Nature’s way of dealing with cancer

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