Glycine and succinic acid are effective indicators of the suppression of epithelial-mesenchymal transition by fucoxanthinol in colorectal cancer stem-like cells

Terasaki, Masaru; Mima, Masatoshi; Kudoh, Satoki; Endo, Tokiko; Maeda, Hayato; Hamada, Junichi; Osada, Kensuke; Miyashita, Kazuo; Mutoh, Michihiro

doi:10.3892/or.2018.6398

Cited by 24 publications

(18 citation statements)

References 40 publications

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“…The disparity of gene expression responses between the 24h and 48h time points for fucoxanthin may indicate that this compound exhibits more complex drug-induced gene expression effects over time than does LY-294002. This hypothesis requires further investigation but is consistent with the observed metabolic lability of fucoxanthin in whole animal studies and the production of a new antiproliferative active metabolite, fucoxanthinol [77]. In parallel experiments not reported here, we have confirmed that fucoxanthinol inhibits U87MG cell proliferation, but do not yet know whether fucoxanthin is extensively metabolized to fucoxanthinol by glioblastoma cells themselves.…”

Section: Plos Onesupporting

confidence: 81%

Transcriptomics predicts compound synergy in drug and natural product treated glioblastoma cells

Pruteanu¹,

Kopanitsa²,

Módos

et al. 2020

PLoS ONE

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Pathway analysis is an informative method for comparing and contrasting drug-induced gene expression in cellular systems. Here, we define the effects of the marine natural product fucoxanthin, separately and in combination with the prototypic phosphatidylinositol 3kinase (PI3K) inhibitor LY-294002, on gene expression in a well-established human glioblastoma cell system, U87MG. Under conditions which inhibit cell proliferation, LY-294002 and fucoxanthin modulate many pathways in common, including the retinoblastoma, DNA damage, DNA replication and cell cycle pathways. In sharp contrast, we see profound differences in the expression of genes characteristic of pathways such as apoptosis and lipid metabolism, contributing to the development of a differentiated and distinctive drug-induced gene expression signature for each compound. Furthermore, in combination, fucoxanthin synergizes with LY-294002 in inhibiting the growth of U87MG cells, suggesting complementarity in their molecular modes of action and pointing to further treatment combinations. The synergy we observe between the dietary nutraceutical fucoxanthin and the synthetic chemical LY-294002 in producing growth arrest in glioblastoma, illustrates the potential of nutripharmaceutical combinations in targeting this challenging disease.

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Section: Plos Onesupporting

confidence: 81%

Transcriptomics predicts compound synergy in drug and natural product treated glioblastoma cells

Pruteanu¹,

Kopanitsa²,

Módos

et al. 2020

PLoS ONE

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“…Our previous studies demonstrated that glycine and succinic acid under normoxia or glycine under hypoxia were metabolite indicators correlated with suppression of sphere formation and epithelial mesenchymal transition due to FxOH treatment in Csps. (25,26) In the present study, the tumor glycine content in the xenograft mice was significantly decreased by Fx administration to 0.5-fold (Fig. 5 and Table 2).…”

Section: Discussionsupporting

confidence: 61%

“…(22–24) We have recently reported that intracellular glycine and succinic acid indices correlated with suppression of sphere formation due to FxOH treatment in Csps. (25,26) Moreover, we have recently demonstrated that FxOH induces apoptosis in Csps and inhibits their tumorigenicity in a xenograft mouse model, (27) while previous studies have not explored differences of biological metabolites in tumor-bearing mice with FxOH or Fx administration.…”

Section: Introductionmentioning

confidence: 99%

Fucoxanthin administration delays occurrence of tumors in xenograft mice by colonospheres, with an anti-tumor predictor of glycine

Terasaki

Matsumoto

Hashimoto

et al. 2019

J. Clin. Biochem. Nutr.

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Fucoxanthin and its major metabolite, fucoxanthinol, have potent anti-cancer properties in carcinogenic model mice and against cancer cells. Evidence has accumulated regarding the diagnostic potential of biological metabolites as invasive and non-invasive obtainable approaches. We recently demonstrated that glycine was an effective predictor of the suppression of sphere formation and epithelial mesenchymal transition by fucoxanthinol in human colorectal cancer stem-like spheroids (colonospheres) under normoxia and hypoxia. In the present study, we investigated the suppressive effect of fucoxanthin on tumorigenesis derived from colonospheres in xenograft mice, and the alteration on the metabolite profiles of mouse tumors by fucoxanthin was evaluated. Fucoxanthin administration at 2.5 mg/kg body weight (p.o.) for 4 weeks significantly inhibited the incidence of tumors by inoculation of colonospheres suspension in BALB/c nu/nu mice compared with control mice, but not tumor sizes. In addition, fucoxanthin down-regulated tumor Cyclin D1 expression by 0.7-fold of that observed in the tumors of the control mice. Moreover, the tumor glycine level in the xenograft mice was decreased by fucoxanthin administration to 0.5-fold. These results imply the possibility of tumor metabolites as a prediction marker of tumorigenicity derived from colorectal cancer stem cells in mice.

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“…Moreover, in a dose-dependent manner, FxOH inhibited sphere formation. These effects were associated with suppressed migration and invasion [104].…”

Section: Xanthophyllsmentioning

confidence: 97%

Carotenoids in Cancer Metastasis—Status Quo and Outlook

et al. 2020

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Metastasis represents a major obstacle in cancer treatment and the leading cause of cancer-related deaths. Therefore, the identification of compounds targeting the multi-step and complex process of metastasis could improve outcomes in the management of cancer patients. Carotenoids are naturally occurring pigments with a plethora of biological activities. Carotenoids exert a potent anti-cancer capacity in various cancer models in vitro and in vivo, mediated by the modulation of signaling pathways involved in the migration and invasion of cancer cells and metastatic progression, including key regulators of the epithelial–mesenchymal transition and regulatory molecules, such as matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), urokinase plasminogen activator (uPA) and its receptor (uPAR), hypoxia-inducible factor-1α (HIF-1α), and others. Moreover, carotenoids modulate the expression of genes associated with cancer progression and inflammatory processes as key mediators of the complex process involved in metastasis. Nevertheless, due to the predominantly preclinical nature of the known anti-tumor effects of carotenoids, and unclear results from certain carotenoids in specific cancer types and/or specific parts of the population, a precise analysis of the anti-cancer effects of carotenoids is essential. The identification of carotenoids as effective compounds targeting the complex process of cancer progression could improve the outcomes of advanced cancer patients.

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Glycine and succinic acid are effective indicators of the suppression of epithelial-mesenchymal transition by fucoxanthinol in colorectal cancer stem-like cells

Cited by 24 publications

References 40 publications

Transcriptomics predicts compound synergy in drug and natural product treated glioblastoma cells

Transcriptomics predicts compound synergy in drug and natural product treated glioblastoma cells

Fucoxanthin administration delays occurrence of tumors in xenograft mice by colonospheres, with an anti-tumor predictor of glycine

Carotenoids in Cancer Metastasis—Status Quo and Outlook

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