Aim: To determine whether 2-(3-carboxy-1-oxopropy1) amino-2-deoxy-D-glucose (COPADG), a derivative of D-amino-glucose, inhibited the growth of human esophageal cancer cell line Eca-109. Methods: Effects of COPADG on Eca-109 cells cultured in RPMI 1640 medium were examined by a tetrazolium-based colorimetric assay (MTT assay). Results: COPADG inhibited the growth of Eca-109 cells in a dose- and time-dependent manner; the maximum inhibition rate was 83.75%. Conclusion: COPADG can directly inhibit the proliferation of Eca-109 cells, which may serve as the experimental evidence for development of new drugs for esophageal cancer therapy. Copyright © 2004 by The WJG.published_or_final_versio

Ji, R

Liu, WM

Lu, H

Qiao, L

Wang, AQ

Wu, J

Xue, QJ

Zhou, Y

World Journal of Gastroenterology

PubMed

HKU Scholars Hub

Title Effect of 2-(3-carboxy-1-oxopropyl) amino-2-deoxy-D-glucose onhuman esophageal cancer cell lineAuthor(s) Wu, J; Lu, H; Zhou, Y; Qiao, L; Ji, R; Wang, AQ; Liu, WM; Xue,QJCitation World Journal Of Gastroenterology, 2004, v. 10 n. 22, p. 3380-3381Issued Date 2004URL http://hdl.handle.net/10722/77376Rights Creative Commons: Attribution 3.0 Hong Kong LicensePO Box 2345, Beijing 100023, China                                                                                                                                                                  World J Gastroenterol  2004;10(22):3380-3381Fax: +86-10-85381893                                                                                                                                                                                                                                 World Journal of GastroenterologyE-mail: wjg@wjgnet.com     www.wjgnet.com                                                                                                                                   Copyright © 2004 by The WJG Press ISSN 1007-9327• BRIEF REPORTS •Effect of 2-(3-carboxy-1-oxopropyl) amino-2-deoxy-D-glucose onhuman esophageal cancer cell lineJing Wu, Hong Lu, Yun Zhou, Liang Qiao, Rui Ji, Ai-Qing Wang, Wei-Min Liu, Qun-Ji XueJing Wu, Ai-Qing Wang, Wei-Min Liu, Qun-Ji Xue, LanzhouInstitute of Chemical Physics, Chinese Academy of Sciences, Lanzhou730000, Gansu Province, ChinaJing Wu, Hong Lu, Yun Zhou, Rui Ji, Department of Gastroenterologyand Hepatology, First Teaching Hospital of Lanzhou Medical College,Lanzhou 730000, Gansu Province, ChinaLiang Qiao, Storr Liver Unit, Westmead Millennium Institute,Department of Gastroenterology and Hepatology, Westmead Hospital,University of Sydney Westmead, NSW 2145, AustraliaCorrespondence to: Dr. Jing Wu, Department of Gastroenterologyand Hepatology, First Teaching Hospital of Lanzhou Medical College,Lanzhou 730000, Gansu Province, China.  wujing36@163.comTelephone: +86-931-8619605Received: 2004-04-22    Accepted: 2004-04-29AbstractAIM: To determine whether 2-(3-carboxy-1-oxopropy1)amino-2-deoxy-D-glucose (COPADG), a derivative of D-amino-glucose, inhibited the growth of human esophagealcancer cell line Eca-109.METHODS: Effects of COPADG on Eca-109 cells culturedin RPMI 1640 medium were examined by a tetrazolium-based colorimetric assay (MTT assay).RESULTS: COPADG inhibited the growth of Eca-109 cellsin a dose- and time-dependent manner; the maximuminhibition rate was 83.75%.CONCLUSION: COPADG can directly inhibit the proliferationof Eca-109 cells, which may serve as the experimentalevidence for development of new drugs for esophagealcancer therapy.Wu J, Lu H, Zhou Y, Qiao L, Ji R, Wang AQ, Liu WM, Xue QJ.Effect of 2-(3-carboxy-1-oxopropyl) amino-2-deoxy-D-glucoseon human esophageal cancer cell line. World J Gastroenterol2004; 10(22): 3380-3381http://www.wjgnet.com/1007-9327/10/3380.aspINTRODUCTION2-(3-carboxy-1-oxopropy1) amino-2-deoxy-D-glucose (COPADG,structure is shown in Figure 1) is a derivative of D-glucose, amonose derivative of degraded chitosan. Previous researches havediscovered that some amino-D-glucose derivatives are capable ofinducing leukemia K562 cells to differentiate into macrophages[1],but their efficacy in inducing apoptosis of tumor cells remainsunclear. We conducted this study to determine whetherCOPADG could inhibit the proliferation of human esophagealcancer cell line Eca-109, to provide experimental evidence fornew drug development for esophageal cancer therapy.MATERIALS AND METHODSMaterialsCOPADG, synthesized by the Lanzhou Institute of ChemicalPhysics of Chinese Academy of Sciences, was dissolved indistilled water, filter-sterilized with 0.22 µm filter disc, and storedat 4  until use. Eca-109 cells were purchased from ShanghaiInstitute of Cell Biology of Chinese Academy of Sciences. RPMI1640 medium, agarose, trypsin and fetal bovine serum (FBS)were obtained from Gibco BRL Company, and the reagents forMTT assay were purchased from Sigma Chemical Co. Ltd.Cell cultureEca-109 cells growing in logarithmic phase were cultured in RPMI1640 medium supplemented with 100 mL/L heat-inactivated FBS,100 µg/mL penicillin and 100 µg/mL streptomycin. The cellswere maintained in a humidified atmosphere containing 50 mL/LCO2 at 37 . The medium was replaced every 48 h.MTT colorimetric assayMTT assay[2] was based on the enzymatic reduction of thetetrazolium salt MTT in viable and metabolically active cells.Cells at 85% to 100% confluency were harvested with themixture of 2.5 g/L trypsin and 0.2 g/L EDTA solution and seededinto a 96-well plate at a density of 4×103 /well, followed byincubation of the cells with COPADG at varied concentrations(0.01-0.09 mol/L) for different lengths of time (24-96 h, Table 1).The control cells were treated in the same way except thatincubation was performed with sterile PBS instead of COPADG.After treatment, the medium was replaced by fresh medium andthe cells were incubated for 4 h with 5 mg/mL MTT, which wasdissolved in 150 µL of 100 g/L DMSO and kept for 1 h. Theoptical densities at 490 nm (A490nm) in the 96-well plates weredetermined using a microplate reader. Cell growth inhibitionwas estimated with the following formula: Growth inhibition(%) =1-A490nm (treated cells)/A490nm (control cells) ×100%.Statistical analysisResults were expressed as mean±SD. Each experiment wasrepeated at least three times. Statistical differences betweeneach group were determined by single-factor analysis ofvariance and correlation analysis using SPSS 11.0 statisticalsoftware.Figure 1  Chemical structure of 2-(3-carboxy-1-oxoprogy1)amino-2-deoxy-D-glucose.RESULTSCOPADG could effectively inhibit the growth of Eca-109 cells,the maximum inhibition rate was 83.75%. The inhibition exhibitedHOHHOOHHOHOH OHNHCOOHan obvious time-and dose-dependent manner when theCOPADG concentrations were below 0.05 mol/L, and higherconcentrations tended to induce gradually stabilized inhibition,suggesting a saturation of the effects of COPADG (Table 1,Figure 2).Figure 2  Inhibition of Eca-109 cell growth by COPADG.DISCUSSIONCOPADG is a derivative of D-glucose, which is a low-molecular-weight compound with multiple biological activities and amonosaccharide derived from chitosan through release of anacetyl group followed by degradation of the residual group.D-glucose is the intermediate during the synthesis of protein-polysaccharide macromolecules, and distributed in almost everyhuman tissue as a part of the structural components of cellmembrane and tissues. From the biological standpoint, D-glucosenot only is involved in hepatic and renal detoxification againsttoxic agents, but also acts to stimulate the anti-inflammatoryresponse and enhance the synthesis of protein-polysaccharides.Studies[3,4] have also shown that D-glucose could inhibit tumorcell growth, and partial derivatives of D-glucose could potentlyinduce differentiation of tumor cells. Some D-amine-glucosederivatives were able to induce leukemia K562 cells todifferentiate into macrophages[5], but this effect failed to beobserved in human hepatocellular carcinoma cell line[1].Currently, COPADG has become a new focus of interest incancer therapy.     By conducting this study, we aimed to test whether COPADG,the newest derivative of D-glucose, had any effect on theproliferation of human esophageal cancer cells. MTT assayshowed that COPADG could effectively inhibit Eca-109 cellTable 1  Inhibitory effect of COPADG on the proliferation of esophageal cancer cell line Eca-109 (mean±SD)Concentra-tion                                 A490nm                   Inhibitory rate (%)      (mol/L)      24 h       48 h        72 h    24 h    48 h    72 h0 (Control) 1.505±0.090 1.686±0.067 1.745±0.077   12.76    20.81    31.290.01 1.313±0.053b 1.336±0.057b 1.199±0.083b   12.76    20.81    31.290.03 0.958±0.028 0.966±0.086 0.900±0.056   36.35    42.68    48.420.05 0.400±0.064b,c 0.429±0.065b,a 0.384±0.050b,c   73.42    74.57    77.990.07 0.383±0.045 0.360±0.039 0.342±0.037   74.55    78.66    80.440.09 0.355±0.046c 0.362±0.053 c 0.280±0.039a   76.41    78.54    83.75At the same time point, P<0.01 vs the control group; bP<0.01 vs 0.03 mol/L; aP<0.05, cP>0.05 vs 0.07 mol/L.proliferation, in a marked time- and dose-dependent mannerbelow the concentration of 0.05 mol/L; the maximum inhibitionrate was 83.75%. The inhibition, however, became stable whenthe concentrations were higher than 0.05 mol/L, indicating thatthe effects of the drug might be saturated at this concentration.      The development of cancer has been considered to be thecombined results of unrestricted cell proliferation and impairmentof normal cell apoptosis[6]. These concepts provide a basisfor the development of new strategies for cancer treatment.Agents with antiproliferative properties and proapoptotic effectshave been widely investigated as potential chemotherapeuticoptions[7,8].        Conclusion, COPADG has obvious time- and concentration-dependent inhibitory effects against the proliferation of humanesophageal cancer cell line Eca-109 in vitro, but whether thiseffect can be achieved in other cell lines still awaits furtherexamination, which may also be necessary to clarify themechanism underlying this effect.REFERENCES1 Wang Z, Qiao Y, Huang GS, Wang AQ, Zhang YQ, Feng JL,Yang GR, Guo Y, Liang R. Glucosamine and glucosaminehydrochloride induced leukemia cell line K562 differentioninto macrophage. Chin Pharmacological Bulletin 2003; 19:290-2932 Mosmann T. Rapid colorimetric assay for cellular growth andsurvival: application to proliferation and cytotoxicity assays. JImmunol Methods 1983; 65: 55-633 McDonnell TJ, Meyn RE, Robertson LE. Implications ofapoptotic cell death regulation in cancer therapy. Semin CancerBiol 1995; 6: 53-604 Xie QL, Dai Y, Sun FY, Lin J, Chen XY, Zhang MY, Chen XJ. Themorphology of  melanoma induced by glucosaminehydrochloride. Anhui Zhongyixueyuan Xuebao 2002; 21: 42-445 Wang Z, Qiao Y, Huang GS, Wang AQ, Zhang YQ, Feng JL,Yang GR, Guo Y, Liang R. Induction of macrophagic differen-tiation of leukemia cell line K562 by N-acetyl-D glucosamine.Disi Junyi Daxue Xuebao 2003; 24: 46-486 Oka Y, Naomoto Y, Yasuoka Y, Hatano H, Haisa M, TanakaN, Orita K. Apoptosis in cultured human colon cancer cellsindued by combined treatments with 5-fluorouracil tumor ne-crosis factor-alpha and interferon-alpha. Jpn J Clin Oncol 1997;27: 231-2357 Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biologicalphenomenon with wide-ranging implications in tissue Kinetics.Br J Cancer 1972; 26: 239-2578 Kerr JF, Winterford CM, Harmon BV. Apoptosis. Its signifi-cance in cancer and cancer therapy. Cancer 1994; 73: 2013-2026Edited by Chen WW and Wang XL  Proofread by Xu FMWu J et al. D-glucose derivative and human esophageal cancer cell line         3381908070605040302010  0Growth inhibition (%)0.01        0.03        0.05       0.07       0.09Concentration (mol/L)244872(h)

Effect of 2-(3-carboxy-1-oxopropyl) amino-2-deoxy-D-glucose on human esophageal cancer cell line

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Effect of 2-(3-carboxy-1-oxopropyl) amino-2-deoxy-D-glucose on human esophageal cancer cell line

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