The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
Masaaki Tokuda - One of the best experts on this subject based on the ideXlab platform.
-
additive antitumour effect of d Allose in combination with cisplatin in non small cell lung cancer cells
Oncology Reports, 2018Co-Authors: Nobuhiro Kanaji, Kazuyo Kamitori, Akram Hossain, Chisato Noguchi, Ayako Katagi, Norimitsu Kadowaki, Masaaki TokudaAbstract:: D‑Allose is a rare sugar which has been shown to have growth inhibitory effects in several kinds of malignancies. However, the effect of D‑Allose on lung cancer progression has not been previously studied. To investigate the antitumour effect of D‑Allose in lung cancer cells and its mechanism, human non-small cell lung cancer (NSCLC) cell lines (squamous cell carcinomas: EBC1 and VMRC‑LCD; adenocarcinomas: A549, HI1017, RERF‑LC‑A1 and NCI-H1975) were treated with D‑Allose (50 mM) with or without cisplatin (5 µM). D‑Allose inhibited cell growth, particularly in EBC1 and VMRC‑LCD cells. In combination with cisplatin, D‑Allose had a synergistic growth inhibitory effect. D‑Allose increased the expression of thioredoxin interacting protein (TXNIP) at mRNA and protein levels. D‑Allose decreased the proportion of cells in G1 phase and increased those in S and G2/M phases. For in vivo experiments, EBC1 cells were inoculated into BALB/c-nu mice. After tumourigenesis, D‑Allose and cisplatin were injected. In this mouse xenograft model, additional treatment with D‑Allose showed a significantly greater tumour inhibitory effect compared with cisplatin alone, accompanied by lower Ki‑67 and higher TXNIP expression. In conclusion, D‑Allose inhibited NSCLC cell proliferation in vitro and tumour progression in vivo. In combination with cisplatin, D‑Allose had an additional antitumour effect. Specifically, increased TXNIP expression and subsequent G2/M arrest play a role in D‑Allose-mediated antitumour effects in NSCLC.
-
combined treatment with d Allose docetaxel and radiation inhibits the tumor growth in an in vivo model of head and neck cancer
Oncology Letters, 2018Co-Authors: Hiroshi Hoshikawa, Kazuyo Kamitori, Kanako Indo, Terushige Mori, Mizuna Kamata, Tomoko Takahashi, Masaaki TokudaAbstract:: The present study was designed to evaluate the effect of one rare sugar, D-Allose, on normal human cells and cutaneous tissue, and to investigate the radiosensitizing and chemosensitizing potential of D-Allose in an in vivo model of head and neck cancer. Results indicated that D-Allose did not inhibit the growth of normal human fibroblasts TIG-1 cells, and no apoptotic changes were observed after D-Allose and D-glucose treatment. The mRNA expression levels of thioredoxin interacting protein (TXNIP) in TIG-1 cells after D-Allose treatment increased by 2-fold (50.4 to 106.5). Conversely, the mRNA expression levels of TXNIP in HSC3 cancer cells increased by 74-fold (1.5 to 110.6), and the thioredoxin (TRX)/TXNIP ratio was markedly reduced from 61.7 to 1.4 following D-Allose treatment. Combined multiple treatments with docetaxel, radiation and D-Allose resulted in the greatest antitumor response in the in vivo model. Hyperkeratosis, epidermal thickening and tumor necrosis factor-α immunostaining were observed following irradiation treatment, but these pathophysiological reactions were reduced following D-Allose administration. Thus, the present findings suggest that D-Allose may enhance the antitumor effects of chemoradiotherapy whilst sparing normal tissues.
-
Additive antitumour effect of D‑Allose in combination with cisplatin in non-small cell lung cancer cells.
Oncology Reports, 2018Co-Authors: Nobuhiro Kanaji, Kazuyo Kamitori, Akram Hossain, Chisato Noguchi, Ayako Katagi, Norimitsu Kadowaki, Masaaki TokudaAbstract:: D‑Allose is a rare sugar which has been shown to have growth inhibitory effects in several kinds of malignancies. However, the effect of D‑Allose on lung cancer progression has not been previously studied. To investigate the antitumour effect of D‑Allose in lung cancer cells and its mechanism, human non-small cell lung cancer (NSCLC) cell lines (squamous cell carcinomas: EBC1 and VMRC‑LCD; adenocarcinomas: A549, HI1017, RERF‑LC‑A1 and NCI-H1975) were treated with D‑Allose (50 mM) with or without cisplatin (5 µM). D‑Allose inhibited cell growth, particularly in EBC1 and VMRC‑LCD cells. In combination with cisplatin, D‑Allose had a synergistic growth inhibitory effect. D‑Allose increased the expression of thioredoxin interacting protein (TXNIP) at mRNA and protein levels. D‑Allose decreased the proportion of cells in G1 phase and increased those in S and G2/M phases. For in vivo experiments, EBC1 cells were inoculated into BALB/c-nu mice. After tumourigenesis, D‑Allose and cisplatin were injected. In this mouse xenograft model, additional treatment with D‑Allose showed a significantly greater tumour inhibitory effect compared with cisplatin alone, accompanied by lower Ki‑67 and higher TXNIP expression. In conclusion, D‑Allose inhibited NSCLC cell proliferation in vitro and tumour progression in vivo. In combination with cisplatin, D‑Allose had an additional antitumour effect. Specifically, increased TXNIP expression and subsequent G2/M arrest play a role in D‑Allose-mediated antitumour effects in NSCLC.
-
d Allose attenuates overexpression of inflammatory cytokines after cerebral ischemia reperfusion injury in gerbil
Journal of Stroke & Cerebrovascular Diseases, 2016Co-Authors: Natsuyo Shinohara, Masaaki Tokuda, Takehiro Nakamura, Takashi Tamiya, Richard F Keep, Aya Shinomiya, Toru Hifumi, Kenya Kawakita, Tohru Yamamoto, Yasuhiro KurodaAbstract:Background The present study investigates the effects of d -Allose, a rare sugar, on the inflammatory response after transient forebrain ischemia in the gerbil and whether it reduces oxidative stress (8-hydroxyl-2′-deoxyguanosine levels) and behavioral deficits. Methods Transient forebrain ischemia was induced by occlusion of the bilateral common carotid arteries for 5 minutes. d -Allose was intraperitoneally injected immediately after ischemia (400 mg/kg). Inflammatory cytokines and oxidative damage in the hippocampus and behavioral deficits were examined 3 days after ischemia. Results d -Allose administration reduced ischemia-induced cytokine production, oxidative stress, and behavioral deficits (motor and memory related). Conclusions The present results suggest that d -Allose reduces brain injury after transient global ischemia by suppressing inflammation as well as by inhibiting oxidative stress.
-
d-Allose Attenuates Overexpression of Inflammatory Cytokines after Cerebral Ischemia/Reperfusion Injury in Gerbil.
Journal of Stroke & Cerebrovascular Diseases, 2016Co-Authors: Natsuyo Shinohara, Masaaki Tokuda, Takehiro Nakamura, Takashi Tamiya, Richard F Keep, Aya Shinomiya, Toru Hifumi, Kenya Kawakita, Tohru YamamotoAbstract:Background The present study investigates the effects of d -Allose, a rare sugar, on the inflammatory response after transient forebrain ischemia in the gerbil and whether it reduces oxidative stress (8-hydroxyl-2′-deoxyguanosine levels) and behavioral deficits. Methods Transient forebrain ischemia was induced by occlusion of the bilateral common carotid arteries for 5 minutes. d -Allose was intraperitoneally injected immediately after ischemia (400 mg/kg). Inflammatory cytokines and oxidative damage in the hippocampus and behavioral deficits were examined 3 days after ischemia. Results d -Allose administration reduced ischemia-induced cytokine production, oxidative stress, and behavioral deficits (motor and memory related). Conclusions The present results suggest that d -Allose reduces brain injury after transient global ischemia by suppressing inflammation as well as by inhibiting oxidative stress.
Ken Izumori - One of the best experts on this subject based on the ideXlab platform.
-
the rare sugar d Allose acts as a triggering molecule of rice defence via ros generation
Journal of Experimental Botany, 2013Co-Authors: Akihito Kano, Ken Izumori, Takeshi Fukumoto, Kouhei Ohtani, Akihide Yoshihara, Toshiaki Ohara, Shigeyuki Tajima, Keiji Tanaka, Takeo Ohkouchi, Yutaka IshidaAbstract:Only d-Allose, among various rare monosaccharides tested, induced resistance to Xanthomonas oryzae pv. oryzae in susceptible rice leaves with defence responses: reactive oxygen species, lesion mimic formation, and PR-protein gene expression. These responses were suppressed by ascorbic acid or diphenylene iodonium. Transgenic rice plants overexpressing OsrbohC, encoding NADPH oxidase, were enhanced in sensitivity to d-Allose. d-Allose-mediated defence responses were suppressed by the presence of a hexokinase inhibitor. 6-Deoxy-d-Allose, a structural derivative of d-Allose unable to be phosphorylated, did not confer resistance. Transgenic rice plants expressing Escherichia coli AlsK encoding d-Allose kinase to increase d-Allose 6-phosphate synthesis were more sensitive to d-Allose, but E. coli AlsI encoding d-Allose 6-phosphate isomerase expression to decrease d-Allose 6-phosphate reduced sensitivity. A d-glucose 6-phosphate dehydrogenase-defective mutant was also less sensitive, and OsG6PDH1 complementation restored full sensitivity. These results reveal that a monosaccharide, d-Allose, induces rice resistance to X. oryzae pv. oryzae by activating NADPH oxidase through the activity of d-glucose 6-phosphate dehydrogenase, initiated by hexokinase-mediated conversion of d-Allose to d-Allose 6-phosphate, and treatment with d-Allose might prove to be useful for reducing disease development in rice.
-
phosphorylation of d Allose by hexokinase involved in regulation of osabf1 expression for growth inhibition in oryza sativa l
Planta, 2013Co-Authors: Takeshi Fukumoto, Ken Izumori, Akihito Kano, Kouhei Ohtani, Akihide Yoshihara, Shigeyuki Tajima, Keiji Tanaka, Megumi Inoue, Yoshio Shigematsu, Takeo OhkouchiAbstract:We previously reported that a rare sugar d-Allose, which is the d-glucose epimer at C3, inhibits the gibberellin-dependent responses such as elongation of the second leaf sheath and induction of α-amylase in embryo-less half seeds in rice (Fukumoto et al. 2011). d-Allose suppresses expressions of gibberellin-responsive genes downstream of SLR1 protein in the gibberellin-signaling through hexokinase (HXK)-dependent pathway. In this study, we discovered that d-Allose induced expression of ABA-related genes including OsNCED1-3 and OsABA8ox1-3 in rice. Interestingly, d-Allose also up-regulated expression of OsABF1, encoding a conserved bZIP transcription factor in ABA signaling, in rice. The d-Allose-induced expression of OsABF1 was diminished by a hexokinase inhibitor, d-mannoheptulose (MNH). Consistently, d-Allose also inhibited Arabidopsis growth, but failed to trigger growth retardation in the glucose-insensitive2 (gin2) mutant, which is a loss-of-function mutant of the glucose sensor AtHXK1. d-Allose activated AtABI5 expression in transgenic gin2 over-expressing wild-type AtHXK1 but not in gin2 over-expressing the catalytic mutant AtHXK1S177A, indicating that the d-Allose phosphorylation by HXK to d-Allose 6-phosphate (A6P) is the first step for the up-regulation of AtABI5 gene expression as well as d-Allose-induced growth inhibition. Moreover, overexpression of OsABF1 showed increased sensitivity to d-Allose in rice. These findings indicated that the phosphorylation of d-Allose at C6 by hexokinase is essential and OsABF1 is involved in the signal transduction for d-Allose-induced growth inhibition.
-
arabidopsis scaffold protein rack1a modulates rare sugar d Allose regulated gibberellin signaling
Plant Signaling & Behavior, 2012Co-Authors: Herman Fennell, Ken Izumori, Abdulquadri Olawin, Rahman Md Mizanur, Jingui Chen, Hemayet UllahAbstract:As energy sources and structural components, sugars are the central regulators of plant growth and development. In addition to the abundant natural sugars in plants, more than 50 different kinds of rare sugars exist in nature, several of which show distinct roles in plant growth and development. Recently, one of the rare sugars, D-Allose, an epimer of D-glucose at C3, is found to suppress plant hormone gibberellin (GA) signaling in rice. Scaffold protein RACK1A in the model plant Arabidopsis is implicated in the GA pathway as rack1a knockout mutants show insensitivity to GA in GA-induced seed germination. Using genetic knockout lines and a reporter gene, the functional role of RACK1A in the D-Allose pathway was investigated. It was found that the rack1a knockout seeds showed hypersensitivity to D-Allose-induced inhibition of seed germination, implicating a role for RACK1A in the D-Allose mediated suppression of seed germination. On the other hand, a functional RACK1A in the background of the double knocko...
-
bioconversion of d fructose to d Allose by novel isomerases
Chinese Journal of Biotechnology, 2012Co-Authors: Xiaobo Li, Ken IzumoriAbstract:: Rare sugar is a kind of important low-energy monosaccharide that is rarely found in nature and difficult to synthesize chemically. D-Allose, a six-carbon aldose, is an important rare sugar with unique physiological functions. It is radical scavenging active and can inhibit cancer cell proliferation. To obtain D-Allose, the microorganisms deriving D-psicose 3-epimerase (DPE) and L-rhamnose isomerase (L-RhI) have drawn intense attention. In this paper, DPE from Clostridium cellulolyticum H10 was cloned and expressed in Bacillus subtilis, and L-RhI from Bacillus subtilis 168 was cloned and expressed in Escherichia coli BL21 (DE3). The obtained crude DPE and L-RhI were then purified through a HisTrap HP affinity chromatography column and an anion-exchange chromatography column. The purified DPE and L-RhI were employed for the production of rare sugars at last, in which DPE catalyzed D-fructose into D-psicose while L-RhI converted D-psicose into D-Allose. The conversion of D-fructose into D-psicose by DPE was 27.34%, and the conversion of D-psicose into D-Allose was 34.64%.
-
Rare sugar d-Allose suppresses gibberellin signaling through hexokinase-dependent pathway in Oryza sativa L.
Planta, 2011Co-Authors: Takeshi Fukumoto, Ken Izumori, Akihito Kano, Kouhei Ohtani, Shigeyuki Tajima, Yumiko Yamasaki-kokudo, Kouji Hosotani, Miu Saito, Chikage Shirakawa, Toshiaki OharaAbstract:One of the rare sugars, d -Allose, which is the epimer of d -glucose at C3, has an inhibitory effect on rice growth, but the molecular mechanisms of the growth inhibition by d -Allose were unknown. The growth inhibition caused by d -Allose was prevented by treatment with hexokinase inhibitors, d -mannoheptulose and N -acetyl- d -glucosamine. Furthermore, the Arabidopsis glucose-insensitive2 ( gin2 ) mutant, which is a loss-of-function mutant of the glucose sensor AtHXK1, showed a d -Allose-insensitive phenotype. d -Allose strongly inhibited the gibberellin-dependent responses such as elongation of the second leaf sheath and induction of α-amylase in embryo-less half rice seeds. The growth of the slender rice1 ( slr1 ) mutant, which exhibits a constitutive gibberellin-responsive phenotype, was also inhibited by d -Allose, and the growth inhibition of the slr1 mutant by d -Allose was also prevented by d -mannoheptulose treatment. The expressions of gibberellin-responsive genes were down-regulated by d -Allose treatment, and the down-regulations of gibberellin-responsive genes were also prevented by d -mannoheptulose treatment. These findings reveal that d -Allose inhibits the gibberellin-signaling through a hexokinase-dependent pathway.
Deok-kun Oh - One of the best experts on this subject based on the ideXlab platform.
-
biotransformation of fructose to Allose by a one pot reaction using flavonifractor plautiid allulose 3 epimerase and clostridium thermocellum ribose 5 phosphate isomerase
Journal of Microbiology and Biotechnology, 2018Co-Authors: Kyungchul Shin, Deok-kun OhAbstract:: D-Allose is a potential medical sugar because it has anticancer, antihypertensive, anti-inflammatory, antioxidative, and immunosuppressant activities. Allose production from fructose as a cheap substrate was performed by a one-pot reaction using Flavonifractor plautiiD-allulose 3-epimerase (FP-DAE) and Clostridium thermocellum ribose 5-phosphate isomerase (CT-RPI). The optimal reaction conditions for Allose production were pH 7.5, 60°C, 0.1 g/l FP-DAE, 12 g/l CT-RPI, and 600 g/l fructose in the presence of 1 mM Co2+. Under these optimized conditions, FP-DAE and CT-RPI produced 79 g/l Allose for 2 h, with a conversion yield of 13%. This is the first biotransformation of fructose to Allose by a two-enzyme system. The production of Allose by a one-pot reaction using FP-DAE and CT-RPI was 1.3-fold higher than that by a two-step reaction using the two enzymes.
-
Microbial metabolism and biotechnological production of d-Allose
Applied Microbiology and Biotechnology, 2011Co-Authors: Deok-kun OhAbstract:d -Allose has attracted a great deal of attention in recent years due to its many pharmaceutical activities, which include anti-cancer, anti-tumor, anti-inflammatory, anti-oxidative, anti-hypertensive, cryoprotective, and immunosuppressant activities. d -Allose has been produced from d -psicose using d -Allose-producing enzymes, including l -rhamnose isomerase, ribose-5-phosphate isomerase, and galactose-6-phosphate isomerase. In this article, the properties, applications, and metabolism of d -Allose are described, and the biochemical properties of d -Allose-producing enzymes and their d -Allose production are reviewed and compared. Moreover, several methods for effective d -Allose production are suggested herein.
-
substrate specificity of a recombinant d lyxose isomerase from providencia stuartii for monosaccharides
Journal of Bioscience and Bioengineering, 2010Co-Authors: Hyunjung Kwon, Soo Jin Yeom, Chang-su Park, Deok-kun OhAbstract:The specific activity and catalytic efficiency (k(cat)/K(m)) of the recombinant putative protein from Providencia stuartii was the highest for D-lyxose among the aldose substrates, indicating that it is a D-lyxose isomerase. Gel filtration analysis suggested that the native enzyme is a dimer with a molecular mass of 44 kDa. The maximal activity for D-lyxose isomerization was observed at pH 7.5 and 45 degrees C in the presence of 1 mM Mn(2+). The enzyme exhibited high isomerization activity for aldose substrates with the C2 and C3 hydroxyl groups in the left-hand configuration, such as D-lyxose, D-mannose, L-ribose, D-talose, and L-Allose (listed in decreasing order of activity). The enzyme exhibited the highest activity for D-xylulose among all pentoses and hexoses. Thus, D-lyxose was produced at 288 g/l from 500 g/l D-xylulose by D-lyxose isomerase at pH 7.5 and 45 degrees C for 2 h, with a conversion yield of 58% and a volumetric productivity of 144 g l(-1) h(-1). The observed k(cat)/K(m) (920 mM(-1) s(-1)) of P. stuartiid-lyxose isomerase for D-xylulose is higher than any of the k(cat)/K(m) values previously reported for sugar and sugar phosphate isomerases with monosaccharide substrates. These results suggest that the enzyme will be useful as an industrial producer of D-lyxose.
-
substrate specificity of a galactose 6 phosphate isomerase from lactococcus lactis that produces d Allose from d psicose
Journal of Biotechnology, 2007Co-Authors: Hayoung Park, Chang-su Park, Deok-kun OhAbstract:Abstract We purified recombinant galactose 6-phosphate isomerase (LacAB) from Lactococcus lactis using HiTrap Q HP and Phenyl-Sepharose columns. The purified LacAB had a final specific activity of 1.79 units/mg to produce d -Allose. The molecular mass of native galactose 6-phosphate isomerase was estimated at 135.5 kDa using Sephacryl S-300 gel filtration, and the enzyme exists as a hetero-octamer of LacA and LacB subunits. The activity of galactose 6-phosphate isomerase was maximal at pH 7.0 and 30 °C, and enzyme activity was independent of metal ions. When 100 g/L of d -psicose was used as the substrate, 25 g/L of d -Allose and 13 g/L of d -altrose were simultaneously produced at pH 7.0 and 30 °C after 12 h of incubation. The enzyme had broad specificity for various aldoses and ketoses. The interconversion of sugars with the same configuration except at the C2 position was driven by using a large amount of enzyme in extended reactions. The interconversion occurred via two isomerization reactions, i.e., the interconversion of d -Allose ↔ d -psicose ↔ d -altrose, and d -Allose to d -psicose reaction was faster than d -altrose to d -psicose reaction.
-
characterization of ribose 5 phosphate isomerase of clostridium thermocellum producing d Allose from d psicose
Biotechnology Letters, 2007Co-Authors: Chang-su Park, Soo Jin Yeom, Deok-kun OhAbstract:The rpiB gene, encoding ribose-5-phosphate isomerase (RpiB) from Clostridium thermocellum, was cloned and expressed in Escherichia coli. RpiB converted d-psicose into d-Allose but it did not convert d-xylose, l-rhamnose, d-altrose or d-galactose. The production of d-Allose by RpiB was maximal at pH 7.5 and 65°C for 30 min. The half-lives of the enzyme at 50°C and 65°C were 96 h and 4.7 h, respectively. Under stable conditions of pH 7.5 and 50°C, 165 g d-Allose l−1 was produced without by-products from 500 g d-psicose l−1 after 6 h.
Kazuyo Kamitori - One of the best experts on this subject based on the ideXlab platform.
-
additive antitumour effect of d Allose in combination with cisplatin in non small cell lung cancer cells
Oncology Reports, 2018Co-Authors: Nobuhiro Kanaji, Kazuyo Kamitori, Akram Hossain, Chisato Noguchi, Ayako Katagi, Norimitsu Kadowaki, Masaaki TokudaAbstract:: D‑Allose is a rare sugar which has been shown to have growth inhibitory effects in several kinds of malignancies. However, the effect of D‑Allose on lung cancer progression has not been previously studied. To investigate the antitumour effect of D‑Allose in lung cancer cells and its mechanism, human non-small cell lung cancer (NSCLC) cell lines (squamous cell carcinomas: EBC1 and VMRC‑LCD; adenocarcinomas: A549, HI1017, RERF‑LC‑A1 and NCI-H1975) were treated with D‑Allose (50 mM) with or without cisplatin (5 µM). D‑Allose inhibited cell growth, particularly in EBC1 and VMRC‑LCD cells. In combination with cisplatin, D‑Allose had a synergistic growth inhibitory effect. D‑Allose increased the expression of thioredoxin interacting protein (TXNIP) at mRNA and protein levels. D‑Allose decreased the proportion of cells in G1 phase and increased those in S and G2/M phases. For in vivo experiments, EBC1 cells were inoculated into BALB/c-nu mice. After tumourigenesis, D‑Allose and cisplatin were injected. In this mouse xenograft model, additional treatment with D‑Allose showed a significantly greater tumour inhibitory effect compared with cisplatin alone, accompanied by lower Ki‑67 and higher TXNIP expression. In conclusion, D‑Allose inhibited NSCLC cell proliferation in vitro and tumour progression in vivo. In combination with cisplatin, D‑Allose had an additional antitumour effect. Specifically, increased TXNIP expression and subsequent G2/M arrest play a role in D‑Allose-mediated antitumour effects in NSCLC.
-
combined treatment with d Allose docetaxel and radiation inhibits the tumor growth in an in vivo model of head and neck cancer
Oncology Letters, 2018Co-Authors: Hiroshi Hoshikawa, Kazuyo Kamitori, Kanako Indo, Terushige Mori, Mizuna Kamata, Tomoko Takahashi, Masaaki TokudaAbstract:: The present study was designed to evaluate the effect of one rare sugar, D-Allose, on normal human cells and cutaneous tissue, and to investigate the radiosensitizing and chemosensitizing potential of D-Allose in an in vivo model of head and neck cancer. Results indicated that D-Allose did not inhibit the growth of normal human fibroblasts TIG-1 cells, and no apoptotic changes were observed after D-Allose and D-glucose treatment. The mRNA expression levels of thioredoxin interacting protein (TXNIP) in TIG-1 cells after D-Allose treatment increased by 2-fold (50.4 to 106.5). Conversely, the mRNA expression levels of TXNIP in HSC3 cancer cells increased by 74-fold (1.5 to 110.6), and the thioredoxin (TRX)/TXNIP ratio was markedly reduced from 61.7 to 1.4 following D-Allose treatment. Combined multiple treatments with docetaxel, radiation and D-Allose resulted in the greatest antitumor response in the in vivo model. Hyperkeratosis, epidermal thickening and tumor necrosis factor-α immunostaining were observed following irradiation treatment, but these pathophysiological reactions were reduced following D-Allose administration. Thus, the present findings suggest that D-Allose may enhance the antitumor effects of chemoradiotherapy whilst sparing normal tissues.
-
Additive antitumour effect of D‑Allose in combination with cisplatin in non-small cell lung cancer cells.
Oncology Reports, 2018Co-Authors: Nobuhiro Kanaji, Kazuyo Kamitori, Akram Hossain, Chisato Noguchi, Ayako Katagi, Norimitsu Kadowaki, Masaaki TokudaAbstract:: D‑Allose is a rare sugar which has been shown to have growth inhibitory effects in several kinds of malignancies. However, the effect of D‑Allose on lung cancer progression has not been previously studied. To investigate the antitumour effect of D‑Allose in lung cancer cells and its mechanism, human non-small cell lung cancer (NSCLC) cell lines (squamous cell carcinomas: EBC1 and VMRC‑LCD; adenocarcinomas: A549, HI1017, RERF‑LC‑A1 and NCI-H1975) were treated with D‑Allose (50 mM) with or without cisplatin (5 µM). D‑Allose inhibited cell growth, particularly in EBC1 and VMRC‑LCD cells. In combination with cisplatin, D‑Allose had a synergistic growth inhibitory effect. D‑Allose increased the expression of thioredoxin interacting protein (TXNIP) at mRNA and protein levels. D‑Allose decreased the proportion of cells in G1 phase and increased those in S and G2/M phases. For in vivo experiments, EBC1 cells were inoculated into BALB/c-nu mice. After tumourigenesis, D‑Allose and cisplatin were injected. In this mouse xenograft model, additional treatment with D‑Allose showed a significantly greater tumour inhibitory effect compared with cisplatin alone, accompanied by lower Ki‑67 and higher TXNIP expression. In conclusion, D‑Allose inhibited NSCLC cell proliferation in vitro and tumour progression in vivo. In combination with cisplatin, D‑Allose had an additional antitumour effect. Specifically, increased TXNIP expression and subsequent G2/M arrest play a role in D‑Allose-mediated antitumour effects in NSCLC.
-
d Allose inhibits cancer cell growth by reducing glut1 expression
Tohoku Journal of Experimental Medicine, 2016Co-Authors: Chisato Noguchi, Kazuyo Kamitori, Akram Hossain, Ayako Katagi, Masaaki Tokuda, Hiroshi Hoshikawa, Youyi Dong, Fuminori YamaguchiAbstract:: Glucose is a major energy source for mammalian cells and is transported into cells via cell-specific expression of various glucose transporters (GLUTs). Especially, cancer cells require massive amounts of glucose as an energy source for their dysregulated growth and thus over-express GLUTs. d-Allose, a C-3 epimer of d-glucose, is one of rare sugars that exist in small quantities in nature. We have shown that d-Allose induces the tumor suppressor gene coding for thioredoxin interacting protein (TXNIP) and inhibits cancer cell growth by G1 cell cycle arrest. It has also been reported that GLUTs including GLUT1 are over-expressed in many cancer cell lines, which may contribute to larger glucose utilization. Since d-Allose suppresses the growth of cancer cells through the upregulation of TXNIP expression, our present study focused on whether d-Allose down-regulates GLUT1 expression via TXNIP expression and thus suppresses cancer cell growth. Western blot and real-time PCR analyses revealed that d-Allose significantly induced TXNIP expression and inhibited GLUT1 expression in a dose-dependent manner in three human cancer cell lines: hepatocellular carcinoma (HuH-7), Caucasian breast adenocarcinoma (MDA-MB-231), and neuroblastoma (SH-SY5Y). In these cell lines, d-Allose treatment inhibited cell growth. Importantly, d-Allose treatment decreased glucose uptake, as measured by the uptake of 2-deoxy d-glucose. Moreover, the reporter assays showed that d-Allose decreased the expression of luciferase through the hypoxia response element present in the tested promoter region. These results suggest that d-Allose may cause the inhibition of cancer growth by reducing both GLUT1 expression and glucose uptake.
-
effects of d Allose in combination with docetaxel in human head and neck cancer cells
International Journal of Oncology, 2014Co-Authors: Kanako Indo, Kazuyo Kamitori, Masaaki Tokuda, Hiroshi Hoshikawa, Fuminori Yamaguchi, Terusige Mori, Nozomu MoriAbstract:: In this study we investigated the combined effects of docetaxel and d-Allose in HSC3 human oral carcinoma cells. The dose enhancement ratios at the 25% survival level were 1.3 and 1.71 for combined treatment with 10 or 25 mM D-Allose, respectively. Apoptosis was significantly increased by addition of D-Allose. Additionally, a synchronous increase in the G(2)/M-phase population was observed after docetaxel plus D-Allose treatment. In vivo experiments revealed that docetaxel plus D-Allose was more effective than either agent alone. Thus, D-Allose enhanced the anticancer effects of docetaxel, and combined treatment may be useful to achieve clinical efficacy with reduced toxicity.
Fuminori Yamaguchi - One of the best experts on this subject based on the ideXlab platform.
-
d Allose inhibits cancer cell growth by reducing glut1 expression
Tohoku Journal of Experimental Medicine, 2016Co-Authors: Chisato Noguchi, Kazuyo Kamitori, Akram Hossain, Ayako Katagi, Masaaki Tokuda, Hiroshi Hoshikawa, Youyi Dong, Fuminori YamaguchiAbstract:: Glucose is a major energy source for mammalian cells and is transported into cells via cell-specific expression of various glucose transporters (GLUTs). Especially, cancer cells require massive amounts of glucose as an energy source for their dysregulated growth and thus over-express GLUTs. d-Allose, a C-3 epimer of d-glucose, is one of rare sugars that exist in small quantities in nature. We have shown that d-Allose induces the tumor suppressor gene coding for thioredoxin interacting protein (TXNIP) and inhibits cancer cell growth by G1 cell cycle arrest. It has also been reported that GLUTs including GLUT1 are over-expressed in many cancer cell lines, which may contribute to larger glucose utilization. Since d-Allose suppresses the growth of cancer cells through the upregulation of TXNIP expression, our present study focused on whether d-Allose down-regulates GLUT1 expression via TXNIP expression and thus suppresses cancer cell growth. Western blot and real-time PCR analyses revealed that d-Allose significantly induced TXNIP expression and inhibited GLUT1 expression in a dose-dependent manner in three human cancer cell lines: hepatocellular carcinoma (HuH-7), Caucasian breast adenocarcinoma (MDA-MB-231), and neuroblastoma (SH-SY5Y). In these cell lines, d-Allose treatment inhibited cell growth. Importantly, d-Allose treatment decreased glucose uptake, as measured by the uptake of 2-deoxy d-glucose. Moreover, the reporter assays showed that d-Allose decreased the expression of luciferase through the hypoxia response element present in the tested promoter region. These results suggest that d-Allose may cause the inhibition of cancer growth by reducing both GLUT1 expression and glucose uptake.
-
effects of d Allose in combination with docetaxel in human head and neck cancer cells
International Journal of Oncology, 2014Co-Authors: Kanako Indo, Kazuyo Kamitori, Masaaki Tokuda, Hiroshi Hoshikawa, Fuminori Yamaguchi, Terusige Mori, Nozomu MoriAbstract:: In this study we investigated the combined effects of docetaxel and d-Allose in HSC3 human oral carcinoma cells. The dose enhancement ratios at the 25% survival level were 1.3 and 1.71 for combined treatment with 10 or 25 mM D-Allose, respectively. Apoptosis was significantly increased by addition of D-Allose. Additionally, a synchronous increase in the G(2)/M-phase population was observed after docetaxel plus D-Allose treatment. In vivo experiments revealed that docetaxel plus D-Allose was more effective than either agent alone. Thus, D-Allose enhanced the anticancer effects of docetaxel, and combined treatment may be useful to achieve clinical efficacy with reduced toxicity.
-
rare sugar d Allose strongly induces thioredoxin interacting protein and inhibits osteoclast differentiation in raw264 cells
Nutrition Research, 2012Co-Authors: Kana Yamada, Kazuyo Kamitori, Chisato Noguchi, Masaaki Tokuda, Youyi Dong, Ikuko Tsukamoto, Yuko Hirata, Mohammad Anwar Hossain, Fuminori YamaguchiAbstract:Abstract Oxidative stress modulates the osteoclast differentiation via redox systems, and thioredoxin 1 (Trx) promotes the osteoclast formation by regulating the activity of transcription factors. The function of Trx is known to be regulated by its binding partner, thioredoxin-interacting protein (TXNIP). We previously reported that the expression of TXNIP gene is strongly induced by a rare sugar d-Allose. In this study, we tested the hypothesis that d-Allose could inhibit the osteoclast differentiation by regulating the Trx function. We used a murine Raw264 cell line that differentiates to the osteoclast by the receptor activator of nuclear factor- κ B ligand (RANKL) treatment. The effect of sugars was evaluated by tartrate-resistant acid phosphatase staining. The expression and localization of TXNIP and Trx protein were examined by Western blotting and immunohistochemisty. The activity of the nuclear factor- κ B, nuclear factor of activated T cells, and activator protein 1 transcription factors was measured by the luciferase reporter assay. The addition of d-Allose (25 mmol/L) inhibited the osteoclast differentiation down to 9.53% ± 1.27% of a receptor activator of nuclear factor- κ B ligand–only treatment. During the osteoclast differentiation, a significant increase of TNXIP was observed by d-Allose treatment. The immunohistochemical analysis showed that both Trx and TXNIP existed in the nucleus in preosteoclasts and osteoclasts. Overexpression of TXNIP by plasmid transfection also inhibited the osteoclast formation, indicating the functional importance of TXNIP for the osteoclast differentiation. Transcriptional activity of the activator protein 1, nuclear factor- κ B, and nuclear factor of activated T cells, known to be modulated by Trx, were inhibited by d-Allose. In conclusion, our data indicate that d-Allose is a strong inhibitor of the osteoclast differentiation, and this effect could be caused by TXNIP induction and a resulting inhibition of the Trx function.
-
growth inhibition of head and neck carcinomas by d Allose
Head and Neck-journal for The Sciences and Specialties of The Head and Neck, 2009Co-Authors: Tomoo Mitani, Kazuyo Kamitori, Masaaki Tokuda, Hiroshi Hoshikawa, Terushige Mori, Fuminori Yamaguchi, Tomohiro Hosokawa, Ikuko Tsukamoto, Nozomu MoriAbstract:Background An inhibitory effect of D-Allose, a rare sugar, on several cancer cell lines has been reported. This study aimed to investigate the growth inhibition of head and neck squamous cell carcinoma cells by D-Allose. Methods We treated 3 head and neck carcinoma cell lines with D-Allose, D-fructose, D-psicose, and D-glucose. Cell growth assays as well as analyses of messenger RNA (mRNA) expression, cell cycle, apoptosis, and uptake of 14C-glucose were performed. Results D-Allose had inhibitory effects on all 3 cell lines and tended to upregulate mRNA expression of glucose transporters, p21 and p53, and downregulate mRNA expression of cyclin A2, cyclin B1, and CDC2. We observed that D-Allose tended to interfere with the intracellular uptake of D-glucose and induced apoptosis. Conclusion Our results indicate that D-Allose inhibits the growth of head and neck squamous cell carcinoma cells. D-Allose has a considerable potential as a new anticancer agent in those patients. © 2009 Wiley Periodicals, Inc. Head Neck, 2009
-
analysis of the inhibitory mechanism of d Allose on molt 4f leukemia cell proliferation
Journal of Bioscience and Bioengineering, 2009Co-Authors: Yuko Hirata, Kazuyo Kamitori, Fuminori Yamaguchi, Youyi Dong, Ikuko Tsukamoto, Madoka Saito, Eisuke Uehara, Ryoji Konishi, Najma Janjua, Masaaki TokudaAbstract:Abstract d -Allose, the C-3 epimer of d -glucose, is one of the rare sugars found in nature. In the present study, we have elucidated for the first time that various leukemia cell lines have different susceptibility to anti-proliferative activity of d -Allose, and that this difference is related to the difference in induction of thioredoxin interacting protein (TXNIP) expression. We examined 5 leukemia cell lines (MOLT-4F, IM-9, HL-60, BALL-1 and Daudi), and found that MOLT-4F (T-cell lymphoblastic leukemia) had the highest susceptibility to d -Allose, and that Daudi (Burkitt's lymphoma) had the lowest. d -Allose significantly slowed the cell cycle progression without causing apoptosis of MOLT-4F cells. Intracellular TXNIP expression was specifically and markedly enhanced in MOLT-4F cells by d -Allose treatment, and subsequent increase of p27 kip1 , a cell cycle inhibitor, was observed. On the other hand, d -Allose did not increase TXNIP and p27 kip1 levels at all in Daudi cells. These results indicate that d -Allose suppresses MOLT-4F cell proliferation possibly by the inhibition of cell cycle progression via induction of TXNIP expression.
