- Volume 16 Issue 5
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Growth of Human Colon Cancer Cells in Nude Mice is Delayed by Ketogenic Diet With or Without Omega-3 Fatty Acids and Medium-chain Triglycerides
- Hao, Guang-Wei (Department General Surgery, Zhongshan Hospital, Fudan University) ;
- Chen, Yu-Sheng (Department General Surgery, Zhongshan Hospital, Fudan University) ;
- He, De-Ming (Department Pathology, Zhongshan Hospital, Fudan University) ;
- Wang, Hai-Yu (Department General Surgery, Zhongshan Hospital, Fudan University) ;
- Wu, Guo-Hao (Department General Surgery, Zhongshan Hospital, Fudan University) ;
- Zhang, Bo (Department General Surgery, Zhongshan Hospital, Fudan University)
- Published : 2015.03.18
Background: Tumors are largely unable to metabolize ketone bodies for energy due to various deficiencies in one or both of the key mitochondrial enzymes, which may provide a rationale for therapeutic strategies that inhibit tumor growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat. Materials and Methods: Thirty-six male BALB/C nude mice were injected subcutaneously with tumor cells of the colon cancer cell line HCT116. The animals were then randomly split into three feeding groups and fed either a ketogenic diet rich in omega-3 fatty acids and MCT (MKD group; n=12) or lard only (LKD group; n=12) or a standard diet (SD group; n=12) ad libitum. Experiments were ended upon attainment of the target tumor volume of
Ketogenic diet;colon cancer;
- Akram M (2013). A focused review of the role of ketone bodies in health and disease. J Med Food, 16, 965-7. https://doi.org/10.1089/jmf.2012.2592
- Amin TT, Suleman W, Al Taissan AA, et al (2012). Patients' profile, clinical presentations and histopathological features of colo-rectal cancer in Al Hassa region, Saudi Arabia. Asian Pac J Cancer Prev, 13, 211-6. https://doi.org/10.7314/APJCP.2012.13.1.211
- Barber MD, Ross JA, Voss AC, Tisdale MJ, Fearon KC (1999). The effect of an oral nutritional supplement enriched with fish oil on weight-loss in patients with pancreatic cancer. Br J Cancer, 81, 80-6. https://doi.org/10.1038/sj.bjc.6690654
- Beck SA, Tisdale MJ (1989). Effect of insulin on weight loss and tumour growth in a cachexia model. Br J Cancer, 59, 677-81. https://doi.org/10.1038/bjc.1989.140
- Berquin IM, Min Y, Wu R, et al (2007). Modulation of prostate cancer genetic risk by omega-3 and omega-6 fatty acids. J Clin Invest, 117, 1866-75. https://doi.org/10.1172/JCI31494
- Connor KM, SanGiovanni JP, Lofqvist C, et al (2007). Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat Med, 13, 868-73. https://doi.org/10.1038/nm1591
- Fearon K, Strasser F, Anker SD, et al (2011). Definition and classification of cancer cachexia: an international consensus. Lancet Oncol, 12, 489-95. https://doi.org/10.1016/S1470-2045(10)70218-7
- Freeman JM, Kossoff EH, Hartman AL (2007). The ketogenic diet: one decade later. Pediatrics, 119, 35-43.
- Giordano KF, Jatoi A (2005). The cancer anorexia/weight loss syndrome: therapeutic challenges. Curr Oncol Rep, 7, 271-6. https://doi.org/10.1007/s11912-005-0050-9
- Hardman WE (2002). Omega-3 fatty acids to augment cancer therapy. J Nutr, 132, 3508-12.
- Hardman WE (2007). Dietary canola oil suppressed growth of implanted MDA-MB 231 human breast tumors in nude mice. Nutr Cancer, 57, 177-83. https://doi.org/10.1080/01635580701277445
- Iftikhar S, Bond AR, Wagan AI, Weinberg PD, Bharath AA (2011). Segmentation of endothelial cell boundaries of rabbit aortic images using a machine learning approach. Int J Biomed Imaging, 2011, 270247.
- Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
- Jin S, DiPaola RS, Mathew R, White E (2007). Metabolic catastrophe as a means to cancer cell death. J Cell Sci, 120, 379-83. https://doi.org/10.1242/jcs.03349
- Jiang YS, Wang FR (2013). Caloric restriction reduces edema and prolongs survival in a mouse glioma model. J Neurooncol, 114, 25-32. https://doi.org/10.1007/s11060-013-1154-y
- Kim HS, Masko EM, Poulton SL, et al (2012). Carbohydrate restriction and lactate transporter inhibition in a mouse xenograft model of human prostate cancer. BJU Int, 110, 1062-9. https://doi.org/10.1111/j.1464-410X.2012.10971.x
- Kimoto Y, Tanji Y, Taguchi T, et al (1998). Antitumor effect of medium-chain triglyceride and its influence on the selfdefense system of the body. Cancer Detect Prev, 22, 219-24. https://doi.org/10.1046/j.1525-1500.1998.0OA32.x
- Kwan HY, Chao X, Su T, et al (2014). Dietary lipids and adipocytes: potential therapeutic targets in cancers. J Nutr Biochem, [Epub ahead of print].
- Lu H, Forbes RA, Verma A (2002). Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis. J Biol Chem, 277, 23111-5. https://doi.org/10.1074/jbc.M202487200
- Lu K, Song XL, Han SL, et al (2014). Potential study perspectives on mechanisms and correlations between adiposity and malignancy. Asian Pac J Cancer Prev, 15, 1057-60. https://doi.org/10.7314/APJCP.2014.15.2.1057
- Masko EM, Thomas JA, Antonelli JA, et al (2010). Lowcarbohydrate diets and prostate cancer: how low is "low enough"? Cancer Prev Res (Phila), 3, 1124-31. https://doi.org/10.1158/1940-6207.CAPR-10-0071
- Mondello P, Mian M, Aloisi C, et al (2015). Cancer cachexia syndrome: pathogenesis, diagnosis, and new therapeutic options. Nutr Cancer, 67, 12-26. https://doi.org/10.1080/01635581.2015.976318
- Mukherjee P, Sotnikov AV, Mangian HJ, et al (1999). Energy intake and prostate tumor growth, angiogenesis, and vascular endothelial growth factor expression. J Natl Cancer Inst, 91, 512-23. https://doi.org/10.1093/jnci/91.6.512
- Nebeling LC, Lerner E (1995). Implementing a ketogenic diet based on medium-chain triglyceride oil in pediatric patients with cancer. J Am Diet Assoc, 95, 693-7. https://doi.org/10.1016/S0002-8223(95)00189-1
- Nebeling LC, Miraldi F, Shurin SB, Lerner E (1995). Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports. J Am Coll Nutr, 14, 202-8. https://doi.org/10.1080/07315724.1995.10718495
- Oleksyszyn J (2011). The complete control of glucose level utilizing the composition of ketogenic diet with the gluconeogenesis inhibitor, the anti-diabetic drug metformin, as a potential anti-cancer therapy. Med Hypotheses, 77, 171-3. https://doi.org/10.1016/j.mehy.2011.04.001
- Otto C, Kaemmerer U, Illert B, et al (2008). Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and mediumchain triglycerides. BMC cancer, 8, 122. https://doi.org/10.1186/1471-2407-8-122
- Paoli A, Cenci L, Grimaldi KA (2011). Effect of ketogenic Mediterranean diet with phytoextracts and low carbohydrates/ high-protein meals on weight, cardiovascular risk factors, body composition and diet compliance in Italian council employees. Nutr J, 10, 112. https://doi.org/10.1186/1475-2891-10-112
- Poff AM, Ari C, Arnold P, Seyfried TN, D'Agostino DP (2014). Ketone supplementation decreases tumor cell viability and prolongs survival of mice with metastatic cancer. Int J Cancer, 135, 1711-20. https://doi.org/10.1002/ijc.28809
- Sawai M, Yashiro M, Nishiguchi Y, Ohira M, Hirakawa K (2004). Growth-inhibitory effects of the ketone body, monoacetoacetin, on human gastric cancer cells with succinyl-CoA: 3-oxoacid CoA-transferase (SCOT) deficiency. Anticancer Res, 24, 2213-7.
- Schmidt M, Pfetzer N, Schwab M, Strauss I, Kammerer U (2011). Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: a pilot trial. Nutr Metab (Lond), 8, 54. https://doi.org/10.1186/1743-7075-8-54
- Seyfried TN, Marsh J, Shelton LM, Huysentruyt LC, Mukherjee P (2012). Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer? Epilepsy Res, 100, 310-26. https://doi.org/10.1016/j.eplepsyres.2011.06.017
- Seyfried TN, Mukherjee P (2005). Targeting energy metabolism in brain cancer: review and hypothesis. Nutr Metab (Lond), 2, 30. https://doi.org/10.1186/1743-7075-2-30
- Sharman MJ, Kraemer WJ, Love DM, et al (2002). A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men. J Nutr, 132, 1879-85.
- Tisdale MJ (1984). Role of acetoacetyl-CoA synthetase in acetoacetate utilization by tumor cells. Cancer Biochem Biophys, 7, 101-7.
- Veech RL (2004). The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostaglandins Leukot Essent Fatty Acids, 70, 309-19. https://doi.org/10.1016/j.plefa.2003.09.007
- Walenta S, Wetterling M, Lehrke M, et al (2000). High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers. Cancer Res, 60, 916-21.
- Wang W, Zhu J, Lyu F, et al (2014). omega-3 Polyunsaturated fatty acids-derived lipid metabolites on angiogenesis, inflammation and cancer. Prostaglandins Other Lipid Mediat, 113-115, 13-20. https://doi.org/10.1016/j.prostaglandins.2014.07.002
- Weidner N, Semple JP, Welch WR, Folkman J (1991). Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma. N Engl J Med, 324, 1-8. https://doi.org/10.1056/NEJM199101033240101
- Xu RH, Pelicano H, Zhou Y, et al (2005). Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia. Cancer Res, 65, 613-21.
- Yang SP, Morita I, Murota SI (1998). Eicosapentaenoic acid attenuates vascular endothelial growth factor-induced proliferation via inhibiting Flk-1 receptor expression in bovine carotid artery endothelial cells. J Cell Physiol, 176, 342-9. https://doi.org/10.1002/(SICI)1097-4652(199808)176:2<342::AID-JCP12>3.0.CO;2-5
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