Xylitol acts as an anticancer monosaccharide to induce selective cancer death via regulation of the glutathione level

Tomonobu, Nahoko; Komalasari, Ni Luh Gede Yoni; Sumardika, I Wayan; Jiang, Fan; Chen, Youyi; Yamamoto, Ken; Kinoshita, Rie; Murata, Hitoshi; Inoue, Yusuke; Sakaguchi, Masakiyo

doi:10.1016/j.cbi.2020.109085

Cited by 26 publications

(19 citation statements)

References 30 publications

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“…The channel protein Sec61 has been demonstrated to import and export ER GSH, and transport is modulated by Bip and Ero1 [ 79 ]. Interestingly, a recent study has shown that xylitol, a compound found in the fungus Cordyceps militaris , may be a promising anticancer therapy via regulation of GSH [ 80 ]. In the proposed mechanism, xylitol induces Bip and CHAC1, resulting in decreased cellular GSH levels, ER stress, and ultimately apoptotic cell death.…”

Section: Glutathione Redox and Ros In Healthy And Tumor Cellsmentioning

confidence: 99%

“…Recently, microenvironment GST has been suggested as important to metastasis and apoptosis in ovarian and bladder cancer [ 99 , 100 ]. Polymorphisms of GSTs have been identified which affect the expression or activity of the enzymes and have been associated with many diseases; some of these have since been proposed as biomarkers of cancer risk and prognosis [ 78 , 79 , 80 ].…”

Section: Glutathione As An Antioxidantmentioning

confidence: 99%

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Role of Glutathione in Cancer: From Mechanisms to Therapies

et al. 2020

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Glutathione (GSH) is the most abundant non-protein thiol present at millimolar concentrations in mammalian tissues. As an important intracellular antioxidant, it acts as a regulator of cellular redox state protecting cells from damage caused by lipid peroxides, reactive oxygen and nitrogen species, and xenobiotics. Recent studies have highlighted the importance of GSH in key signal transduction reactions as a controller of cell differentiation, proliferation, apoptosis, ferroptosis and immune function. Molecular changes in the GSH antioxidant system and disturbances in GSH homeostasis have been implicated in tumor initiation, progression, and treatment response. Hence, GSH has both protective and pathogenic roles. Although in healthy cells it is crucial for the removal and detoxification of carcinogens, elevated GSH levels in tumor cells are associated with tumor progression and increased resistance to chemotherapeutic drugs. Recently, several novel therapies have been developed to target the GSH antioxidant system in tumors as a means for increased response and decreased drug resistance. In this comprehensive review we explore mechanisms of GSH functionalities and different therapeutic approaches that either target GSH directly, indirectly or use GSH-based prodrugs. Consideration is also given to the computational methods used to describe GSH related processes for in silico testing of treatment effects.

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Section: Glutathione Redox and Ros In Healthy And Tumor Cellsmentioning

confidence: 99%

Section: Glutathione As An Antioxidantmentioning

confidence: 99%

Role of Glutathione in Cancer: From Mechanisms to Therapies

et al. 2020

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“…Its sweetness is equal to that of sucrose [ 16 ]. It has anti-cariogenic properties [ 21 , 22 ], anti-inflammatory effects [ 23 , 24 ], and was recently found to inhibit lung cancer cell proliferation [ 23 ] and induce apoptosis in melanoma cells [ 25 , 26 ]. Interestingly, our previous in vitro studies demonstrated that partial substitution of glucose in culture media with xylitol significantly suppressed the proliferation of oral cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Partial Substitution of Glucose with Xylitol Prolongs Survival and Suppresses Cell Proliferation and Glycolysis of Mice Bearing Orthotopic Xenograft of Oral Cancer

et al. 2022

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Many types of cancer have metabolic alterations with increased glycolysis. Identification of alternative sweeteners that do not fuel cancer is a novel approach to cancer control. The present study aimed to investigate the effects of xylitol on tumor growth and survival of mice bearing orthotopic xenograft of tongue cancers. The results showed that partial substitution of glucose with xylitol (glucose 0.35 g plus xylitol 2.06 g/kg body weight) non-significantly reduced tumor volume, and significantly prolonged the median survival time from 19 days in the control to 30.5 days in the xylitol group. Immunohistochemical data of the tongue tissue shows significantly lower intense-to-mild staining ratios of the proliferation marker Ki-67 in the xylitol than those of the control group (p = 0.04). Furthermore, the xylitol substitution significantly reduced the expression of the rate-limiting glycolytic enzyme, phosphofructokinase-1 (PFK-1) (p = 0.03), and showed a non-significant inhibition of PFK activity. In summary, partial substitution of glucose with xylitol at the equivalent dose to human household use of 10 g/day slows down tumor proliferation and prolongs survival of mice bearing an orthotopic oral cancer xenograft, possibly through glycolytic inhibition, with minimal adverse events. The insight warrants clinical studies to confirm xylitol as a candidate sweetener in food products for cancer survivors.

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“…Entre suas principais propriedades farmacológicas estão a prevenção de cáries e infecções de ouvido (ZACHARIS, 2012), além de ser quimicamente menos reativo do que suas correspondentes aldoses/cetoses, dificultando a clivagem dos microrganismos e obtenção de energia (DASGUPTA et al, 2017). Quando extraído do microrganismo Cordyceps militaris, o xilitol demonstrou também ação anticâncer, por meio do estresse oxidativo causado às células cancerígenas, levando-as à morte celular apoptótica (TOMONOBU et al, 2020).…”

Section: Introductionunclassified

Efeito de diferentes embalagens no armazenamento de doce em massa de araçá amarelo (Psidium cattleianum Sabine) adoçado com xilitol

Vieira¹,

Oliveira²,

Matias³

et al. 2021

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O estudo da estabilidade de novos produtos oriundos do processamento de frutas nativas subutilizadas é essencial para o desenvolvimento da indústria nacional. O objetivo foi avaliar o efeito de diferentes embalagens sobre a estabilidade físico-química de doce em massa de araçá amarelo adoçado com xilitol. A polpa de araçá foi avaliada quanto aos parâmetros físico-químicos de qualidade e seguiu para o processamento do doce. O doce foi elaborado com 60% de polpa, 40% de xilitol, 2% de pectina de Baixo Teor de Metoxilação e 0,12% de cloreto de cálcio, sendo acondicionado em quatro tipos de embalagens (polipropileno, vidro, filme PVC e filme PVC recoberto com alumínio). A estabilidade do doce foi avaliada, durante 90 dias de armazenamento a temperatura ambiente (27,5 ºC), sendo realizadas as análises de qualidade a cada 30 dias. O teor de água e sólidos totais do doce diferiram significativamente entre os tipos de embalagens para os tempos de 30, 60 e 90 dias. Assim, a migração da água para o ambiente ocorreu mais facilmente nos doces embalados em polipropileno, filme PVC recoberto com alumínio e filme PVC, devido as características físicas da matriz polimérica das embalagens plásticas. Para o pH, entre 30 e 90 dias de armazenamento apenas a embalagem de filme PVC recoberto com alumínio não apresentou-se estável. Infere-se que o doce em massa de araçá é um produto inovador, e que o armazenamento a temperatura ambiente em embalagem de vidro transparente com tampa metálica até 90 dias é o mais viável.

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Xylitol acts as an anticancer monosaccharide to induce selective cancer death via regulation of the glutathione level

Cited by 26 publications

References 30 publications

Role of Glutathione in Cancer: From Mechanisms to Therapies

Role of Glutathione in Cancer: From Mechanisms to Therapies

Partial Substitution of Glucose with Xylitol Prolongs Survival and Suppresses Cell Proliferation and Glycolysis of Mice Bearing Orthotopic Xenograft of Oral Cancer

Efeito de diferentes embalagens no armazenamento de doce em massa de araçá amarelo (Psidium cattleianum Sabine) adoçado com xilitol

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