Effects of CLIC4 on Fucoxanthinol-Induced Apoptosis in Human Colorectal Cancer Cells

Yokoyama, Reo; Kojima, Hiroyuki; Takai, Rie; Ohta, Tohru; Maeda, Hayato; Miyashita, Kazuo; Mutoh, Michihiro; Terasaki, Masaru

doi:10.1080/01635581.2020.1779760

Cited by 10 publications

(11 citation statements)

References 34 publications

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“…In the present study, FxOH treatment inhibited the cell cycle in HaPC-5 cells (Figures 3B and 8). The effects of cell cycle arrest by FxOH or Fx in cancer cells were previously found in various cancer cell lines (20,28,29). As was observed in pancreatic cancer cells, cell-cycle arrest followed by apoptosis induction may be a common feature of various cancer cells.…”

Section: Discussionmentioning

confidence: 57%

“…Regarding FxOH, it suppressed tumorigenesis in immunodeficient NOD-SCID mice (24). It also induced apoptosis in colon cancer cells and colon cancer stem-like spheroids through attenuation of integrin, mitogen-activated protein kinase (MAPK), nuclear factor-ĸB, phosphatidylinositol-3 kinase/protein kinase B (PI3K/AKT), peroxisome proliferator-activated receptor, signal transducers and activators of transcription (STAT), chloride intracellular channel 4 (CLIC4), and caspase signaling (25)(26)(27)(28). These molecules are also involved in migration, invasion, epithelial-mesenchymal transition, and cell-cycle arrest.…”

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confidence: 99%

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Effect of Fucoxanthinol on Pancreatic Ductal Adenocarcinoma Cells from anN-Nitrosobis(2-oxopropyl)amine-initiated Syrian Golden Hamster Pancreatic Carcinogenesis Model

Terasaki

Nishizaka

Murase

et al. 2021

Cancer Genomics Proteomics

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Background/Aim: Fucoxanthinol (FxOH) is a marine carotenoid metabolite with potent anti-cancer activity. However, little is known about the efficacy of FxOH in pancreatic cancer. In the present study, we investigated the inhibitory effect of FxOH on six types of cells cloned from amine (BOP)-induced hamster pancreatic cancer (HaPC) cells. Materials and Methods: FxOH action and its molecular mechanisms were investigated in HaPC cells using flow-cytometry, comprehensive gene array, and western blotting analyses. Results: FxOH (5.0 μM) significantly suppressed the growth of four out of six types of HaPC cells. Moreover, FxOH significantly suppressed cell cycle, chemokine, integrin, actin polymerization, microtubule organization and PI3K/AKT and TGF-β signals, and activated caspase-3 followed by apoptosis and anoikis induction in HaPC-5 cells. Conclusion: FxOH may have a high potential as a cancer chemopreventive agent in a hamster pancreatic carcinogenesis model.Pancreatic cancer is one of the most lethal cancers worldwide because it is treatment resistant and has aggressive potential for metastasis/invasion with resultant poor prognosis. From the GLOBOCAN 2018 estimates, 432,242 pancreatic cancer deaths occur per year (4.5% of total) (1), and the 5-year survival rate remains poor at 10% (2). Accumulating evidence suggests that aberrant network integrity of gene mutation, gene methylation, transcriptome, microRNA, non-coding RNA, proteome, tumor microenvironment, and immune cells are crucial for human pancreatic cancer development. In particular, highly carcinogenic point mutations in driver genes, such as KRAS, CDKN2A, TP53, and SMAD4, are observed in many specimens (3-7). Pancreatic intraepithelial neoplasia (PanIN) is a premalignant lesion in pancreatic carcinogenesis and has the stepwise progress graded as four types from mild to severe. KRAS, CDKN2A, TP53 and SMAD4 are somatically mutated in turn along with the malignant progression of PanIN, followed by the cancer progression (8).N-nitrosobis(2-oxopropyl)amine (BOP)-treated Syrian golden hamsters are a chemical carcinogenesis model that represents human pancreatic cancer because it induces PanIN, and pancreatic ductal adenocarcinoma resembles human pancreatic cancer, which also includes similar genetic mutations such as in K-ras, CDKN2A, and SMAD4 (9). Therefore, the BOP-induced hamster pancreatic cancer 407 This article is freely accessible online.

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Section: Discussionmentioning

confidence: 57%

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confidence: 99%

Effect of Fucoxanthinol on Pancreatic Ductal Adenocarcinoma Cells from anN-Nitrosobis(2-oxopropyl)amine-initiated Syrian Golden Hamster Pancreatic Carcinogenesis Model

Terasaki

Nishizaka

Murase

et al. 2021

Cancer Genomics Proteomics

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“…In addition, FxOH reduced the activation of CLIC4 and FAK and changed the expression and distribution of integrin β1. When the CLIC4 gene was knocked out, the apoptosis-inducing effect of FxOH almost disappeared, indicating that CLIC4 may be involved in FxOH-induced apoptosis, and FxOH can induce anoikis in CRC cells by inhibiting integrin signaling [65,66]. At the same time, FxOH weakened the epithelial-mesenchymal transition (EMT), inhibited the activation of MAPK and Stat signals, and altered metabolite profiles in CRC cells [67].…”

Section: Carotenoidsmentioning

confidence: 99%

Natural Marine Products: Anti-Colorectal Cancer In Vitro and In Vivo

Han

2022

Marine Drugs

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Colorectal cancer, a malignant tumor with high mortality, has a poor prognosis due to drug resistance and toxicity in clinical surgery and chemotherapy. Thus, finding safer and more efficient drugs for clinical trials is vital and urgent. Natural marine compounds, with rich resources and original chemical structures, are applied widely in anticancer treatments. We provide a systematic overview of recently reported marine compounds such as alkaloids, peptides, terpenoids, polysaccharides, and carotenoids from in vitro, in vivo, and clinical studies. The in vitro studies summarized the marine origins and pharmacological mechanisms, including anti-proliferation, anti-angiogenesis, anti-migration, anti-invasion, the acceleration of cycle arrest, and the promotion of tumor apoptosis, of various compounds. The in vivo studies outlined the antitumor effects of marine compounds on colorectal cancer model mice and evaluated their efficacy in terms of tumor inhibition, hepatotoxicity, and nephrotoxicity. The clinical studies summarized the major chemical classifications and targets of action of the clinical drugs that have entered clinical approval and completed approval for marine anticancer. In summary, we present the current situation regarding the application of natural anti-colorectal cancer marine compounds and prospects for their clinical application.

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“…In addition, the protein expression of cyclin D1, cyclin D2, integrin α5, integrin β1, phospho-Paxillin(Tyr 31 ), phospho-AKT(Ser 473 ), phospho-C-Raf (Ser 338 ), phospho-MEK1/2(Ser 217/221 ), PPARγ and phospho-Smad2(Ser 465/467 ) was downregulated, while that of phospho-ERK1/2(Thr 202 /Tyr 204 ) and NRF2 was upregulated [ 84 ]. We also demonstrated the suppressive effect of CLIC4 signal and induction of anoikis due to attenuation of an integrin signal by FxOH in DLD-1 cells [ 85 , 86 ]. Tamura et al showed that FxOH (10 μM) induced apoptosis in HCT116 cells by increasing the NF-κB activity.…”

Section: Effect By Brown Algae and Fx In Crc Cellular Linesmentioning

confidence: 99%

Fucoxanthin and Colorectal Cancer Prevention

Terasaki

Kubota

Kojima

et al. 2021

Cancers

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Colorectal cancer (CRC), which ranks among the top 10 most prevalent cancers, can obtain a good outcome with appropriate surgery and/or chemotherapy. However, the global numbers of both new cancer cases and death from CRC are expected to increase up to 2030. Diet-induced lifestyle modification is suggested to be effective in reducing the risk of human CRC; therefore, interventional studies using diets or diet-derived compounds have been conducted to explore the prevention of CRC. Fucoxanthin (Fx), a dietary carotenoid, is predominantly contained in edible brown algae, such as Undaria pinnatifida (wakame) and Himanthalia elongata (Sea spaghetti), which are consumed particularly frequently in Asian countries but also in some Western countries. Fx is responsible for a majority of the anticancer effects exerted by the lipophilic bioactive compounds in those algae. Interventional human trials have shown that Fx and brown algae mitigate certain risk factors for CRC; however, the direct mechanisms underlying the anti-CRC properties of Fx remain elusive. Fx and its deacetylated type “fucoxanthinol” (FxOH) have been reported to exert potential anticancer effects in preclinical cancer models through the suppression of many cancer-related signal pathways and the tumor microenvironment or alteration of the gut microbiota. We herein review the most recent studies on Fx as a potential candidate drug for CRC prevention.

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Effects of CLIC4 on Fucoxanthinol-Induced Apoptosis in Human Colorectal Cancer Cells

Cited by 10 publications

References 34 publications

Effect of Fucoxanthinol on Pancreatic Ductal Adenocarcinoma Cells from anN-Nitrosobis(2-oxopropyl)amine-initiated Syrian Golden Hamster Pancreatic Carcinogenesis Model

Effect of Fucoxanthinol on Pancreatic Ductal Adenocarcinoma Cells from anN-Nitrosobis(2-oxopropyl)amine-initiated Syrian Golden Hamster Pancreatic Carcinogenesis Model

Natural Marine Products: Anti-Colorectal Cancer In Vitro and In Vivo

Fucoxanthin and Colorectal Cancer Prevention

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