Dietary glucosylceramides suppress tumor growth in a mouse xenograft model of head and neck squamous cell carcinoma by the inhibition of angiogenesis through an increase in ceramide

Yazama, Hiroaki; Kitatani, Kazuyuki; Fujiwara, Kazunori; Kato, Masatane; Hashimoto-Nishimura, Mayumi; Kawamoto, Katsuyuki; Hasegawa, Kensaku; Kitano, Hiroya; Bielawska, Alicja; Bielawski, Jacek; Okazaki, Toshiro

doi:10.1007/s10147-014-0734-y

Cited by 22 publications

(17 citation statements)

References 38 publications

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“…Sphingolipids and ceramides were the only groups of lipid-related biochemicals that were decreased in maternal plasma due to diabetes mellitus. Regulation of the sphingolipid and ceramide pathway affects angiogenesis and impairs endothelial function and the remodelling of maternal spiral arteries that occurs in preeclampsia [52,53]. Preeclampsia is associated with diabetes mellitus [54,55].…”

Section: Diabetic Dysregulation Of Maternal and Embryonic Lipid Metabmentioning

confidence: 99%

Metabolic Profiling in Blastocoel Fluid and Blood Plasma of Diabetic Rabbits

Schindler

Pendzialek

Grybel

et al. 2020

IJMS

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Metabolic disorders of the mother adversely affect early embryo development, causing changes in maternal metabolism and consequent alterations in the embryo environment in the uterus. The goal of this study was to analyse the biochemical profiles of embryonic fluids and blood plasma of rabbits with and without insulin-dependent diabetes mellitus (DT1), to identify metabolic changes associated with maternal diabetes mellitus in early pregnancy. Insulin-dependent diabetes was induced by alloxan treatment in female rabbits 10 days before mating. On day 6 post-coitum, plasma and blastocoel fluid (BF) were analysed by ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) (Metabolon Inc. Durham, NC, USA). Metabolic datasets comprised a total of 284 and 597 compounds of known identity in BF and plasma, respectively. Diabetes mellitus had profound effects on maternal and embryonic metabolic profiles, with almost half of the metabolites changed. As predicted, we observed an increase in glucose and a decrease in 1,5-anhydroglucitol in diabetic plasma samples. In plasma, fructose, mannose, and sorbitol were elevated in the diabetic group, which may be a way of dealing with excess glucose. In BF, metabolites of the pentose metabolism were especially increased, indicating the need for ribose-based compounds relevant to DNA and RNA metabolism at this very early stage of embryo development. Other changes were more consistent between BF and plasma. Both displayed elevated acylcarnitines, body3-hydroxybutyrate, and multiple compounds within the branched chain amino acid metabolism pathway, suggesting that lipid beta-oxidation is occurring at elevated levels in the diabetic group. This study demonstrates that maternal and embryonic metabolism are closely related. Maternal diabetes mellitus profoundly alters the metabolic profile of the preimplantation embryo with changes in all subclasses of metabolites.

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Section: Diabetic Dysregulation Of Maternal and Embryonic Lipid Metabmentioning

confidence: 99%

Metabolic Profiling in Blastocoel Fluid and Blood Plasma of Diabetic Rabbits

Schindler

Pendzialek

Grybel

et al. 2020

IJMS

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“…For example, the dietary intake of glucosylceramide prevents colon preneoplastic lesions [15] and head and neck cancers [16,17]. Also, when administered to the skin, it improves skin disorders [18].…”

Section: Introductionmentioning

confidence: 99%

Chemical Analysis of the Sugar Moiety of Monohexosylceramide Contained in Koji, Japanese Traditional Rice Fermented with Aspergillus

et al. 2016

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Koji, rice fermented with Aspergillus, is used for saccharification of starch contained in crops during the manufacturing of many of Japanese traditional foods and drinks. Japanese people have long eaten koji, and many beneficial substances have been reported to be contained in koji. However, there has been no report on the existence or content of galactosylceramide in koji. To address this issue, we analyzed the chemical composition of the sugar moiety of monohexosylceramide contained in koji, and elucidate that 30.3% of yellow koji is galactosylceramide, 69.7% of that is glucosylceramide, 19.2% of white koji is galactosylceramide, and 80.8% of that is glucosylceramide. This is the first report of the existence and content of galactosylceramide in koji.

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“…24 Further, dietary Glu-Cer suppressed tumor growth in a mouse xenograft model of HNSCC by inhibiting angiogenesis through an increase in ceramide, and dietary Glu-Cer was synthesized by a de novo pathway after digestion absorption, thus raising the blood level of ceramide. 25 The inhibitory effect of Glu-Cer on colon tumorigenesis has previously been reported. Inamine et al showed that dietary Glu-Cer had potential chemopreventive effects in short-term colon carcinogenesis bioassays in rats, inhibiting the formation of preneoplastic lesions such as aberrant crypt foci and β-catenin-accumulated crypts.…”

Section: Introductionmentioning

confidence: 87%

Inhibitory Effects of Glucosylceramide on Tumorigenesis Induced by a Carcinogen in Mice

et al. 2019

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Objective: Glucosylceramide (Glu-Cer), a glycosylated form of ceramide, has been reported to have cytotoxic effects in the cells of various cancers. We previously reported that dietary Glu-Cer from rice bran had inhibitory effects on human head and neck squamous cell carcinoma (HNSCC) in nonobese diabetes (NOD)/severe combined immunodeficiency (SCID) mice. In HNSCC, preventing recurrence and second primary cancer is required to improve prognosis. The purpose of the present study was to determine whether dietary Glu-Cer had anticarcinogenic and antitumorigenic effects in a mouse model of HNSCC. Methods: A total of 40 CB6F1-Tg rasH2@Jcl mice were divided into two groups: control and Glu-Cer. All mice were given 4-nitroquinoline 1-oxide for 24 weeks. Control group mice were fed the normal diet without Glu-Cer. The Glu-Cer group mice were given a mixture of the normal diet plus 0.25% Glu-Cer for 24 weeks. Microscopic examination was performed to identify grossly visible preneoplasms and neoplasms in the mouth, pharynx, and esophagus. Epithelial regions were classified as normal tissue, carcinoma in situ (CIS), or SCC; and the number of each type of region was counted. Results: Compared with the Glu-Cer group mice, control group mice more frequently developed individual and multiple tumors of each type, including CIS and SCC, in the mouth, pharynx, or esophagus. Conclusion: Tumor development was effectively inhibited by dietary Glu-Cer derived from rice bran, indicating that this and related compounds show promise as prophylactic agents for human HNSCC.

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Dietary glucosylceramides suppress tumor growth in a mouse xenograft model of head and neck squamous cell carcinoma by the inhibition of angiogenesis through an increase in ceramide

Abstract: These results suggest that dietary glucosylceramides trigger the de novo pathway of ceramide synthesis, indicating that sphingosine-based ceramide suppresses the growth of head and neck tumors through the inhibition of pro-angiogenic signals such as VEGF, VEGF receptor-2, and HIF-1α.

Cited by 22 publications

References 38 publications

Metabolic Profiling in Blastocoel Fluid and Blood Plasma of Diabetic Rabbits

Metabolic Profiling in Blastocoel Fluid and Blood Plasma of Diabetic Rabbits

Chemical Analysis of the Sugar Moiety of Monohexosylceramide Contained in Koji, Japanese Traditional Rice Fermented with Aspergillus

Inhibitory Effects of Glucosylceramide on Tumorigenesis Induced by a Carcinogen in Mice

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