No effect of dietary aspartame or stevia on pancreatic acinar carcinoma development, growth, or induced mortality in a Murine model

Frontiers in Oncology

Volumn 7, Issue FEB, 2017, Pages

  Dooley, James ^a,b   Lagou, Vasiliki ^a,b   Dresselaers, Tom ^c   van Dongen, Katinka A ^a,b   Himmelreich, Uwe ^c   Liston, Adrian ^a,b  

^a DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^b UNIVERSITY OF LEUVEN   (Belgium)

^c DEPARTMENT OF IMAGING AND PATHOLOGY   (Belgium)

Author keywords

Aspartame; In vivo; MRI; Pancreatic cancer; Stevia

Indexed keywords

ASPARTAME DERIVATIVE;

ACINAR CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER GROWTH; CANCER MORTALITY; CELL MATURATION; DIABETES MELLITUS; DIET RESTRICTION; MALE; MOUSE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; NUTRITIONAL ASSESSMENT; OBESITY; ORAL GLUCOSE TOLERANCE TEST; PANCREAS CARCINOMA; PUBLIC HEALTH; STEVIA;

EID: 85014799805     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2017.00018     Document Type: Article

References (39)

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin (2016) 66(1):7-30. doi: 10.3322/caac.21332
2. Bardeesy N, DePinho RA. Pancreatic cancer biology and genetics. Nat Rev Cancer (2002) 2(12):897-909. doi:10.1038/nrc949
3. Whitcomb DC, Shelton CA, Brand RE. Genetics and genetic testing in pancreatic cancer. Gastroenterology (2015) 149(5):1252-64.e4. doi:10.1053/j.gastro.2015.07.057
4. Li X, Staszewski L, Xu H, Durick K, Zoller M, Adler E. Human receptors for sweet and umami taste. Proc Natl Acad Sci U S A (2002) 99(7):4692-6. doi:10.1073/pnas.072090199
5. Soffritti M, Belpoggi F, Manservigi M, Tibaldi E, Lauriola M, Falcioni L, et al. Aspartame administered in feed, beginning prenatally through life span, induces cancers of the liver and lung in male Swiss mice. Am J Ind Med (2010) 53(12):1197-206. doi:10.1002/ajim.20896
6. Soffritti M, Belpoggi F, Tibaldi E, Esposti DD, Lauriola M. Life-span exposure to low doses of aspartame beginning during prenatal life increases cancer effects in rats. Environ Health Perspect (2007) 115(9):1293-7. doi:10.1289/ehp.10271
7. Magnuson B, Williams GM. Carcinogenicity of aspartame in rats not proven. Environ Health Perspect (2008) 116(6):A239-40; author reply A40. doi:10.1289/ehp.10881
8. Schernhammer ES, Bertrand KA, Birmann BM, Sampson L, Willett WC, Feskanich D. Consumption of artificial sweetener- and sugar-containing soda and risk of lymphoma and leukemia in men and women. Am J Clin Nutr (2012) 96(6):1419-28. doi:10.3945/ajcn.111.030833
9. Andreatta MM, Munoz SE, Lantieri MJ, Eynard AR, Navarro A. Artificial sweetener consumption and urinary tract tumors in Cordoba, Argentina. Prev Med (2008) 47(1):136-9. doi:10.1016/j.ypmed.2008.03.015
10. Drake I, Sonestedt E, Gullberg B, Ahlgren G, Bjartell A, Wallstrom P, et al. Dietary intakes of carbohydrates in relation to prostate cancer risk: a prospective study in the Malmo diet and cancer cohort. Am J Clin Nutr (2012) 96(6):1409-18. doi:10.3945/ajcn.112.039438
11. Lim U, Subar AF, Mouw T, Hartge P, Morton LM, Stolzenberg-Solomon R, et al. Consumption of aspartame-containing beverages and incidence of hematopoietic and brain malignancies. Cancer Epidemiol Biomarkers Prev (2006) 15(9):1654-9. doi:10.1158/1055-9965.EPI-06-0203
12. Bosetti C, Gallus S, Talamini R, Montella M, Franceschi S, Negri E, et al. Artificial sweeteners and the risk of gastric, pancreatic, and endometrial cancers in Italy. Cancer Epidemiol Biomarkers Prev (2009) 18(8):2235-8. doi:10.1158/1055-9965.EPI-09-0365
13. Gallus S, Scotti L, Negri E, Talamini R, Franceschi S, Montella M, et al. Artificial sweeteners and cancer risk in a network of case-control studies. Ann Oncol (2007) 18(1):40-4. doi:10.1093/annonc/mdl346
14. Magnuson BA, Burdock GA, Doull J, Kroes RM, Marsh GM, Pariza MW, et al. Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies. Crit Rev Toxicol (2007) 37(8):629-727. doi:10.1080/10408440701516184
15. Mallikarjun S, Sieburth RM. Aspartame and risk of cancer: a meta-analytic review. Arch Environ Occup Health (2015) 70(3):133-41. doi:10.1080/19338244.2013.828674
16. Butchko HH, Stargel WW, Comer CP, Mayhew DA, Benninger C, Blackburn GL, et al. Aspartame: review of safety. Regul Toxicol Pharmacol (2002) 35(2 Pt 2):S1-93. doi:10.1006/rtph.2002.1542
17. Soffritti M, Padovani M, Tibaldi E, Falcioni L, Manservisi F, Belpoggi F. The carcinogenic effects of aspartame: the urgent need for regulatory re-evaluation. Am J Ind Med (2014) 57(4):383-97. doi:10.1002/ajim.22296
18. Tandel KR. Sugar substitutes: health controversy over perceived benefits. J Pharmacol Pharmacother (2011) 2(4):236-43. doi:10.4103/0976-500X.85936
19. Goyal SK, Samsher, Goyal RK. Stevia (Stevia rebaudiana) a bio-sweetener: a review. Int J Food Sci Nutr (2010) 61(1):1-10. doi:10.3109/09637480903193049
20. Ulbricht C, Isaac R, Milkin T, Poole EA, Rusie E, Grimes Serrano JM, et al. An evidence-based systematic review of stevia by the Natural Standard Research Collaboration. Cardiovasc Hematol Agents Med Chem (2010) 8(2):113-27. doi:10.2174/187152510791170960
21. Yasukawa K, Kitanaka S, Seo S. Inhibitory effect of stevioside on tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin. Biol Pharm Bull (2002) 25(11):1488-90. doi:10.1248/bpb.25.1488
22. Takasaki M, Konoshima T, Kozuka M, Tokuda H, Takayasu J, Nishino H, et al. Cancer preventive agents. Part 8: chemopreventive effects of stevioside and related compounds. Bioorg Med Chem (2009) 17(2):600-5. doi:10.1016/j.bmc.2008.11.077
23. Tevethia MJ, Bonneau RH, Griffith JW, Mylin L. A simian virus 40 large T-antigen segment containing amino acids 1 to 127 and expressed under the control of the rat elastase-1 promoter produces pancreatic acinar carcinomas in transgenic mice. J Virol (1997) 71(11):8157-66.
24. Ornitz DM, Hammer RE, Messing A, Palmiter RD, Brinster RL. Pancreatic neoplasia induced by SV40 T-antigen expression in acinar cells of transgenic mice. Science (1987) 238(4824):188-93. doi:10.1126/science.2821617
25. Teno JM, Harrell FE Jr, Knaus W, Phillips RS, Wu AW, Connors A Jr, et al. Prediction of survival for older hospitalized patients: the HELP survival model. Hospitalized Elderly Longitudinal Project. J Am Geriatr Soc (2000) 48(5 Suppl):S16-24. doi:10.1111/j.1532-5415.2000.tb03126.x
26. Harrington DP, Fleming TR. A class of rank test procedures for censored survival-data. Biometrika (1982) 69(3):553-66. doi:10.1093/biomet/69.3.553
27. Zhang T, Gan Z, Gao C, Ma L, Li Y, Li X, et al. Occurrence of artificial sweeteners in human liver and paired blood and urine samples from adults in Tianjin, China and their implications for human exposure. Environ Sci Process Impacts (2016) 18(9):1169-76. doi:10.1039/c6em00130k
28. Paolini M, Vivarelli F, Sapone A, Canistro D. Aspartame, a bittersweet pill. Carcinogenesis (2016). doi:10.1093/carcin/bgw025
29. Mann TS, Agnihotri VK, Kumar D, Pal PK, Koundal R, Kumar A, et al. In vitro cytotoxic activity guided essential oil composition of flowering twigs of Stevia rebaudiana. Nat Prod Commun (2014) 9(5):715-8.
30. Ukiya M, Sawada S, Kikuchi T, Kushi Y, Fukatsu M, Akihisa T. Cytotoxic and apoptosis-inducing activities of steviol and isosteviol derivatives against human cancer cell lines. Chem Biodivers (2013) 10(2):177-88. doi:10.1002/cbdv.201200406
31. Mizushina Y, Akihisa T, Ukiya M, Hamasaki Y, Murakami-Nakai C, Kuriyama I, et al. Structural analysis of isosteviol and related compounds as DNA polymerase and DNA topoisomerase inhibitors. Life Sci (2005) 77(17):2127-40. doi:10.1016/j.lfs.2005.03.022
32. Lopez V, Perez S, Vinuesa A, Zorzetto C, Abian O. Stevia rebaudiana ethanolic extract exerts better antioxidant properties and antiproliferative effects in tumour cells than its diterpene glycoside stevioside. Food Funct (2016) 7(4):2107-13. doi:10.1039/c5fo01586c
33. Chen JM, Ding L, Sui XC, Xia YM, Wan HD, Lu T. Production of a bioactive sweetener steviolbioside via specific hydrolyzing ester linkage of stevioside with a beta-galactosidase. Food Chem (2016) 196:155-60. doi:10.1016/j.foodchem.2015.09.035
34. Paul S, Sengupta S, Bandyopadhyay TK, Bhattacharyya A. Stevioside induced ROS-mediated apoptosis through mitochondrial pathway in human breast cancer cell line MCF-7. Nutr Cancer (2012) 64(7):1087-94. doi:10.1080/01635581.2012.712735
35. Koyama E, Kitazawa K, Ohori Y, Izawa O, Kakegawa K, Fujino A, et al. In vitro metabolism of the glycosidic sweeteners, stevia mixture and enzymatically modified stevia in human intestinal microflora. Food Chem Toxicol (2003) 41(3):359-74. doi:10.1016/S0278-6915(03)00039-5
36. Davis DL, Ganter L, Weinkle J. Aspartame and incidence of brain malignancies. Cancer Epidemiol Biomarkers Prev (2008) 17(5):1295-6. doi:10.1158/1055-9965.EPI-07-2869
37. Kuzma JN, Cromer G, Hagman DK, Breymeyer KL, Roth CL, Foster-Schubert KE, et al. No difference in ad libitum energy intake in healthy men and women consuming beverages sweetened with fructose, glucose, or high-fructose corn syrup: a randomized trial. Am J Clin Nutr (2015) 102(6):1373-80. doi:10.3945/ajcn.115.116368
38. Schernhammer ES, Hu FB, Giovannucci E, Michaud DS, Colditz GA, Stampfer MJ, et al. Sugar-sweetened soft drink consumption and risk of pancreatic cancer in two prospective cohorts. Cancer Epidemiol Biomarkers Prev (2005) 14(9):2098-105. doi:10.1158/1055-9965.EPI-05-0059
39. Hampton T. Sugar substitutes linked to weight gain. JAMA (2008) 299(18):2137-8. doi:10.1001/jama.299.18.2137