Cilostazol and enzymatically modified isoquercitrin attenuate experimental colitis and colon cancer in mice by inhibiting cell proliferation and inflammation

Kangawa, Yumi; Yoshida, Toshinori; Maruyama, Kiyoshi; Okamoto, Minako; Kihara, Tohru; Nakamura, Michi; Ochiai, Masako; Hippo, Yoshitaka; Hayashi, Shim-mo; Shibutani, Makoto

doi:10.1016/j.fct.2016.12.018

Cited by 24 publications

(8 citation statements)

References 78 publications

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“…Paraffin‐embedded tissue sections stained with H&E were used to diagnose the proliferative lesions in the mouse colon. The proliferative lesions were histopathologically classified as dysplasia, adenoma, and adenocarcinoma . Immunofluorescence was carried out using methanol‐fixed snap‐frozen sections of colon tissues obtained from the mice 18‐20 weeks after their i.p.…”

Section: Methodsmentioning

confidence: 99%

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Fluorescence tumor imaging by i.v. administered indocyanine green in a mouse model of colitis‐associated colon cancer

et al. 2018

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Fluorescence tumor imaging using exogenous fluorescent tumor‐targeting agents has potential to improve early tumor detection. The fluorescent contrast agent indocyanine green (ICG) is used in medical diagnostics. The aim of the present study is to investigate the tumor imaging capability and the imaging mechanism of i.v. administered ICG in a mouse model of colitis‐associated colon cancer. To do this, an azoxymethane/dextran sodium sulfate‐induced colon cancer mouse model was used. Ex vivo imaging experiments were carried out 1 hour after i.v. injection of ICG. The ICG fluorescence was observed in the colon tumor tissues, with sufficient tumor to normal tissue ratio, correlating with tumor malignancy. In the tumor tissues, ICG fluorescence was localized in the vascular interstitial tissue. Immunofluorescence microscopy revealed that tumor cells formed tight junctions normally, suggesting an inability of tumor cellular uptake of ICG. In contrast, tumor tissues increased the CD31‐immunoreactive endothelial cell area, and accumulated stromal cells immunoreactive for COX‐2 and tumor cell population immunoreactive for inducible nitric oxide synthase. In vivo vascular permeability assay revealed that prostaglandin E2 promoted the endothelial cell permeability of ICG. In conclusion, our data indicated that fluorescence contrast‐enhanced imaging following i.v. administered ICG can be applied to the detection of colon tumors in a mouse colitis‐associated colon cancer model. The tumor tissue preference of ICG in the present model can be attributed to the enhanced vascular leakage of ICG involving inflammatory mediators, such as COX‐2 and inducible nitric oxide synthase, in conjunction with increased tumor vascularity.

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Section: Methodsmentioning

confidence: 99%

“…The proliferative lesions were histopathologically classified as dysplasia, adenoma, and adenocarcinoma. 30,31 Immunofluorescence was carried out using methanol-fixed snap-frozen sections of colon tissues obtained from the mice 18-20 weeks after their i.p. injection of AOM.…”

Section: Histology and Immunofluorescencementioning

confidence: 99%

Fluorescence tumor imaging by i.v. administered indocyanine green in a mouse model of colitis‐associated colon cancer

et al. 2018

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“…Table 3 provides a summary of the role of anthocyanins in CRC cell lines or animal models. Anthocyanin-enriched fractions from black raspberry inhibited cell growth in HT-29 and HCT-119 cells [57,67,69,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93]. In CRC, an anthocyanin-enriched extract of black raspberry showed effects similar to black raspberry powder on CRC cell lines in suppressing cell proliferation, inducing apoptosis, decreasing the activity of DNMT1 and DNMT3B and of demethylate CDKN2A, SFRP2, SFRP5 and WIF1 in the Wnt pathway [60,71].…”

Section: Chemoprevention Of Colorectal Cancer In Inflammatory Bowementioning

confidence: 99%

Chemopreventive Effects of Strawberry and Black Raspberry on Colorectal Cancer in Inflammatory Bowel Disease

2019

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Colorectal cancer (CRC) remains the third most common cause of cancer-related death in the United States and the fourth globally with a rising incidence. Inflammatory bowel disease (IBD) is a chronic immunologically mediated disease that imposes a significant associated health burden, including the increased risk for colonic dysplasia and CRC. Carcinogenesis has been attributed to chronic inflammation and associated with oxidative stress, genomic instability, and immune effectors as well as the cytokine dysregulation and activation of the nuclear factor kappa B (NFκB) signaling pathway. Current anti-inflammation therapies used for IBD treatment have shown limited effects on CRC chemoprevention, and their long-term toxicity has limited their clinical application. However, natural food-based prevention approaches may offer significant cancer prevention effects with very low toxicity profiles. In particular, in preclinical and clinical pilot studies, strawberry and black raspberry have been widely selected as food-based interventions because of their potent preventive activities. In this review, we summarize the roles of strawberry, black raspberry, and their polyphenol components on CRC chemoprevention in IBD.

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Section: Introductionmentioning

confidence: 99%

“…AGIQ has been found to possess a higher bioavailability than quercetin or isoquercitrin in humans 10 and has proven pharmacological benefits in vivo, including tumor suppressive and anti-oxidative effects. [11][12][13][14][15][16][17][18][19] AGIQ has been used as a natural food additive in Japan since 1987 and is in wide use as an anti-oxidant in a large number of products, ranging from beverages, frozen dairy products and puddings to chewing gums and canned soups. 20 Following the Japanese approval in 1996, the Expert Panel of the Flavor and Extract Manufacturers Association granted AGIQ a generally recognized as safe status in 2005, and the same status was granted by the US Food and Drug Administration (FDA) in 2007.…”

Section: Introductionmentioning

confidence: 99%

Ten-day and four-week toxicity and toxicokinetics studies of alpha-glycosyl isoquercitrin in juvenile Göttingen minipigs

Maronpot

Ramot

Koyanagi

et al. 2019

Toxicology Research and Application

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Background: Alpha-glycosyl isoquercitrin (AGIQ) is widely used as an anti-oxidative food additive in many products. Nevertheless, information on its safety and toxicity is still very limited. A 90-day toxicity study in rats and comprehensive genotoxic studies have proven AGIQ to be safe. Aim: The goal of this study was to assess the safety of use of AGIQ in infant formula. To test for potential adverse effects on growth or other safety issues specific for young animals, we performed a 10-day and a 4-week study in preweaning Gö ttingen minipigs. Method: Newborn minipigs were treated four times per day with oral AGIQ (0, 100, 300, or 1000 mg/kg/day) for 10 days or 4 weeks. Results: All animals remained in good health throughout both studies, and there were no treatment-related signs of toxicity or abnormal findings in blood parameters. In the 4-week study, yellow coloration of the bones was seen in all animals in the high-dose group with no related histological findings. Hepatocellular and sinusoidal/Kupffer cell iron deposition was seen in the liver of all animals in both studies, as expected after the routine administration of supplemental iron to newborn animals. There was sufficient evidence of systemic exposure based on plasma levels of AGIQ metabolites. Conclusion: Taken together, these findings show that oral administration of AGIQ in reconstituted milk supplement to preweaning Gö ttingen minipigs for 4 weeks at up to 1000 mg/ kg/day does not result in any adverse treatment-related effects and further support the safety of AGIQ as a food additive.

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Cilostazol and enzymatically modified isoquercitrin attenuate experimental colitis and colon cancer in mice by inhibiting cell proliferation and inflammation

Cited by 24 publications

References 78 publications

Fluorescence tumor imaging by i.v. administered indocyanine green in a mouse model of colitis‐associated colon cancer

Fluorescence tumor imaging by i.v. administered indocyanine green in a mouse model of colitis‐associated colon cancer

Chemopreventive Effects of Strawberry and Black Raspberry on Colorectal Cancer in Inflammatory Bowel Disease

Ten-day and four-week toxicity and toxicokinetics studies of alpha-glycosyl isoquercitrin in juvenile Göttingen minipigs

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