Viability, Migration Rate, and mRNA Expression of GLUT5, GLUT7, GLUT11 in WiDr Colorectal Cancer Cell Line
Abstract
BACKGROUND: Insufficient glucose levels in colorectal cancer (CRC) patients leads to a condition where fructose might become an alternative source for cells proliferation, but the role of fructose or fructose-glucose combinations in development of CRC has not been elucidated well. In this study, the effect of fructose-glucose variations on viability, migration, and glucose transporter (GLUT)5, GLUT7, GLUT11 mRNA expressions in WiDr CRC cell line were examined.
METHODS: Cells were treated with varying ratios of fructose-glucose (F100%; F75%:G25%; F50%:G50%; F25%:G75%; G100%; F: Fructose, G: Glucose). Untreated cells (F0:G0) were used as cell control. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used for cell viability test, scratch assay was used to examine the cell migration, and quantitative polymerase chain reaction (qPCR) was performed to examine mRNA expressions. Data were analyzed using one-way analysis of variance (ANOVA) and followed with Tukey's post-hoc test, with p<0.05 consideres as significant.
RESULTS: Fructose-glucose combinations and glucose 100% significantly increased the cell viability compared to control (p<0.05). All treatment groups showed a significant increase in cell migration compared to control (p=0.000). Only GLUT7 and GLUT11 expressions in the G100% group were significantly different compared to the control (p=0.000). GLUT7 and GLUT11 expressions were also significantly different in F100% and F50%:G50% treatments compared to G100% (p=0.000).
CONCLUSION: Taken together, fructose might play important role in cell migration. However, in cell viability, combination with glucose could increase fructose's effect. Fructose might not affect the mRNA expressions of GLUT5, GLUT7 and GLUT11.
KEYWORDS: GLUT5, GLUT7, GLUT11, fructose transporter, colorectal cancer, WiDr
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Lin X, Xiao Z, Chen T, Liang SH, Guo H. Glucose metabolism on tumor plasticity, diagnosis, and treatment. Front Oncol. 2020; 10: 317, CrossRef.
Jonoush M, Fathi S, Ardekanizadeh NH. The association between different types of dietary carbohydrates and colorectal cancer: A case-control study. Front Nutr. 2022; 9: 898337. doi: 10.3389/fnut.2022.898337, CrossRef.
Aran V, Victorino AP, Thuler LC, Ferreira CG. Colorectal cancer: Epidemiology, disease mechanisms and interventions to reduce onset and mortality. Clin Colorectal Cancer. 2016; 15(3): 195-203, CrossRef.
Bu P, Chen KY, Xiang K, Johnson C, Crown SB, Rakhilin N, et al. Aldolase B-mediated fructose metabolism drives metabolic reprogramming of colon cancer liver metastasis. Cell Metab. 2018; 27(6): 1249-62.e4, CrossRef.
Krause N, Wegner A. Fructose metabolism in cancer. Cells. 2020; 9(12): 2635, CrossRef.
Sohn EJ, Kim JH, Oh SO, Kim JY. Regulation of self-renewal in ovarian cancer stem cells by fructose via chaperone-mediated autophagy. Biochim Biophys Acta Mol Basis Dis. 2023; 1869(6): 166723, CrossRef.
Ismail A, Tanasova M. Importance of GLUT transporters in disease diagnosis and treatment. Int J Mol Sci. 2022; 23(15): 8698, CrossRef.
Park GB, Jeong JY, Kim D. GLUT5 regulation by AKT1/3-miR-125b-5p downregulation induces migratory activity and drug resistance in TLR-modified colorectal cancer cells. Carcinogenesis. 2020; 41(10): 1329-40, CrossRef.
Barron CC, Bilan PJ, Tsakiridis T, Tsiani E. Facilitative glucose transporters: Implications for cancer detection, prognosis and treatment. Metabolism. 2016; 65(2): 124-39, CrossRef.
Navale AM, Paranjape AN. Glucose transporters: Physiological and pathological roles. Biophys Rev. 2016; 8(1): 5-9, CrossRef.
Ahmed D, Eide PW, Eilertsen IA, Danielsen SA, Eknæs M, Hektoen M, et al. Epigenetic and genetic features of 24 colon cancer cell lines. Oncogenesis. 2013; 2(9): e71. doi: 10.1038/oncsis.2013.35, CrossRef.
American Type Culture Collection [Internet]. WiDr CCL-218™ [cited 2023 Apr 13]. Available from: https://www.atcc.org/.
Jiang W, He T, Liu S, Zheng Y, Xiang L, Pei X, et al. The PIK3CA E542K and E545K mutations promote glycolysis and proliferation via induction of the β-catenin/SIRT3 signaling pathway in cervical cancer. J Hematol Oncol. 2018; 11(1): 139, CrossRef.
Hadi S, Porjo LA, Sandra F. Mechanism and potential therapy in ameloblastoma: Akt signaling pathway. Indones Biomed J. 2022; 14(1): 1-10, CrossRef.
Utami DH, Nugraheni N, Jenie RI, Meiyanto E. Co-treatment of Brazilein enhances cytotoxicity of doxorubicin on WiDr colorectal cancer cells through cell cycle arrest. Indones Biomed J. 2020; 12(4): 376-83, CrossRef.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods. 2001; 25(4): 402-8, CrossRef.
Wang G, Wang JJ, Yin PH, Xu K, Wang YZ, Shi F, et al. New strategies for targeting glucose metabolism–mediated acidosis for colorectal cancer therapy. J Cell Physiol. 2019; 234(1): 348-68, CrossRef.
Jang C, Hui S, Lu W, Cowan AJ, Morscher RJ, Liu W, et al. The small intestine converts dietary fructose into glucose and organic acids. Cell Metab. 2018; 27(2): 351-61, CrossRef.
Zargaraan A, Kamaliroosta L, Yaghoubi AS, Mirmoghtadaie L. Effect of substitution of sugar by high fructose corn syrup on the physicochemical properties of bakery and dairy products: A review. Nutr Food Sci Res. 2016; 3(4): 3-11, CrossRef.
Goncalves MD, Lu C, Tutnauer J, Hartman TE, Hwang SK, Murphy CJ, et al. High-fructose corn syrup enhances intestinal tumor growth in mice. Science. 2019; 363(6433): 1345-9, CrossRef.
Nakagawa T, Lanaspa MA, Millan IS, Fini M, Rivard CJ, Sanchezlozada LG, et al. Fructose contributes to the Warburg effect for cancer growth. Cancer Metab. 2020; 8: 16, CrossRef.
Nakagawa T, Johnson RJ, Andres-Hernando A, Roncal-Jimenez C, Sanchez-Lozada LG, Tolan DR, et al. Fructose production and metabolism in the kidney. J Am Soc Nephrol. 2020; 31(5): 898-906, CrossRef.
Pramesthi ADED, Ardana M, Indriyanti N. Drug-herb interaction between metformin and Momordica charantia in diabetic mice. Mol Cell Biomed Sci. 2019; 3(2): 81-7, CrossRef.
Kim J, Kang J, Kang YL, Woo J, Kim Y, Huh J, et al. Ketohexokinase-A acts as a nuclear protein kinase that mediates fructose-induced metastasis in breast cancer. Nat Commun. 2020; 11: 5436, CrossRef.
Gauer JS, Tumova S, Lippiat JD, Kerimi A, Williamson G. Differential patterns of inhibition of the sugar transporters GLUT2, GLUT5 and GLUT7 by flavonoids. Biochem Pharmacol. 2018; 152: 11-20, CrossRef.
Manolescu A, Salas-burgos AM, Fischbarg J, Cheeseman CI. Identification of a hydrophobic residue as a key determinant of fructose transport by the facilitative hexose transporter SLC2A7 (GLUT7). J Biol Chem. 2005; 280(52): 42978-83, CrossRef.
Ferreira RS, Pons JL, Labesse G. Insights into substrate and inhibitor selectivity among human GLUT transporters through comparative modeling and molecular docking. ACS Omega. 2019; 4(3): 4748-60, CrossRef.
Scheepers A, Schmidt S, Manolescu A, Cheeseman CI, Bell A, Zahn C, et al. Characterization of the human SLC2A11 (GLUT11) gene: Alternative promoter usage, function, expression, and subcellular distribution of three isoforms, and lack of mouse orthologue. Mol Membr Biol. 2005; 22(4): 339-51, CrossRef.
Chen C, Ma J, Lu R, Wang Y, Zhao J, Al CET. Perturbated glucose metabolism augments epithelial cell proinflammatory function in chronic rhinosinusitis. J Allergy Clin Immunol. 2023; 151(4): 991-1004.e20, CrossRef.
Mcbrayer SK, Cheng JC, Singhal S, Krett NL, Rosen ST, Shanmugam M. Multiple myeloma exhibits novel dependence on GLUT4, GLUT8, and GLUT11: Implications for glucose transporter-directed therapy. Blood. 2012; 119(20): 4686-97, CrossRef.
Chadt A, Al-Hasani H. Glucose transporters in adipose tissue, liver, and skeletal muscle in metabolic health and disease. Pflügers Arch Eur J Physiol. 2020; 472(9): 1273-98, CrossRef.
Koepsell H. Glucose transporters in the small intestine in health and disease. Pflügers Arch Eur J Physiol. 2020; 472(9): 1207-48, CrossRef.
Mesonero J, Matosin M, Cambier D, Brot-laroche E. Sugar-dependent expression of the fructose transporter GLUT5 in Caco-2 cells. Biochem J. 1995; 312(Pt 3): 757-62, CrossRef.
Lizuka K. Recent progress on fructose metabolism-Chrebp, fructolysis, and polyol pathway. Nutrients. 2023; 15(7): 1778, CrossRef.
Abílio AP, Abudasse G, Kampango A, Candrinho B, Sitoi S, Luciano J, et al. Distribution and breeding sites of Aedes aegypti and Aedes albopictus in 32 urban/peri-urban districts of Mozambique: implication for assessing the risk of arbovirus outbreaks. PLoS Negl Trop Dis. 2018; 12(9): e0006692, CrossRef.
National Center for Biotechnology Information. l-Alanyl-l-glutamine [Internet]. PubChem Compound Summary for CID 123935 [cited 2023 Apr 13]. Available from: https://pubchem.ncbi.nlm.nih.gov/.
DOI: https://doi.org/10.18585/inabj.v15i5.2534
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