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http://dx.doi.org/10.7314/APJCP.2015.16.18.8053

Potential Benefit of Metformin as Treatment for Colon Cancer: the Evidence so Far  

Abdelsatir, Azza Ali (Histocenter)
Husain, Nazik Elmalaika (Department of Pathology, Faculty of Medicine and Health Sciences, Omdurman Islamic University)
Hassan, Abdallah Tarig (Department of Pharmacy, Blue Nile Pharmaceuticals)
Elmadhoun, Wadie M (Nile Valley University)
Almobarak, Ahmed O (Department of Pathology, Faculty of Medicine, University of Medical Sciences and Technology)
Ahmed, Mohamed H (Department of Medicine, Milton Keynes University Hospital NHS Foundation Trust)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.18, 2016 , pp. 8053-8058 More about this Journal
Abstract
Metformin is known as a hypoglycaemic agent that regulates glucose homeostasis by inhibiting liver glucose production and increasing muscle glucose uptake. Colorectal cancer (CRC) is one of the most common cancers worldwide, with about a million new cases diagnosed each year. The risk factors for CRC include advanced age, smoking, black race, obesity, low fibre diet, insulin resistance, and the metabolic syndrome. We have searched Medline for the metabolic syndrome and its relation to CRC, and metformin as a potential treatment of colorectal cancer. Administration of metformin alone or in combination with chemotherapy has been shown to suppress CRC. The mechanism that explains how insulin resistance is associated with CRC is complex and not fully understood. In this review we have summarised studies which showed an association with the metabolic syndrome as well as studies which tackled metformin as a potential treatment of CRC. In addition, we have also provided a summary of how metformin at the cellular level can induce changes that suppress the activity of cancer cells.
Keywords
Metformin; colon cancer; obesity and insulin resistance;
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1 Aleksandrova K, Boeing H, Jenab M, et al (2011). Metabolic syndrome and risks of colon and rectal cancer: the European prospective investigation into cancer and nutrition study. Cancer Prev Res, 4, 1873-83.   DOI
2 Buzzai M, Jones R, Amaravadi R, et al (2007). Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth. Cancer Res, 67, 6745-52.   DOI
3 Cho Y, Ko B, Kim S, et al (2014). Does metformin affect the incidence of colonic polyps and adenomas in patients with type 2 diabetes mellitus? Intest Res, 12, 139-45.   DOI
4 Donohoe C, O'farrell N, Doyle S, Reynolds J (2014). The role of obesity in gastrointestinal cancer: evidence and opinion. Therap Adv Gastroenterol, 7, 38-50.   DOI
5 Giovannucci E, Pollak M, Platz E, et al (2000). A prospective study of plasma insulin-like growth factor-1 and binding protein-3 and risk of colorectal neoplasia in women. Cancer Epidemiol Biomarkers Prev, 9, 345-9.
6 Grimberg A & Cohen P (2000). Role of insulin-like growth factors and their binding proteins in growth control and carcinogenesis. J Cell Physiol, 183, 1-9.   DOI
7 Handelsman Y, Leroith D, Bloomgarden Z, et al (2013). Diabetes and cancer--an AACE/ACE consensus statement. Endocr Pract, 19, 675-93.   DOI
8 Higurashi T, Takahashi H, Endo H, et al (2012). Metformin efficacy and safety for colorectal polyps: a double-blind randomized controlled trial. BMC Cancer, 12, 118.   DOI
9 Hillon P, Guiu B, Vincent J, Petit J (2010). Obesity, type 2 diabetes and risk of digestive cancer. Gastroenterol Clin Biol, 34, 529-33.   DOI
10 Hsu Y, Chiu H, Liou J, et al (2012). Glycated hemoglobin A1c is superior to fasting plasma glucose as an independent risk factor for colorectal neoplasia. Cancer Causes Control, 23, 321-8.   DOI
11 Sanchez N, Stierman B, Saab S, et al (2012). Physical activity reduces risk for colon polyps in a multiethnic colorectal cancer screening population. BMC Res Notes, 5, 312.   DOI
12 Sandhu M, Dunger D, Giovannucci E (2002). Insulin, insulinlike growth factor-I (IGF-I), IGF binding proteins, their biologic interactions, and colorectal cancer. J Natl Cancer Inst, 94, 972-80.   DOI
13 Saydah SH, Platz EA, Rifai N, et al (2003). Association of markers of insulin and glucose control with subsequent colorectal cancer risk. Cancer Epidemiol Biomarkers Prev, 12, 412-8.
14 Schoenalgire C, Amrein L, Zakikhani M, Panasci L & Pollak M (2010). Metformin blocks the stimulative effect of a high-energy diet on colon carcinoma growth in vivo and is associated with reduced expression of fatty acid synthase. Endocr Relat Cancer, 17, 351-60.   DOI
15 Spillane S, Bennett K, Sharp L, Barron T (2014). Metformin exposure and disseminated disease in patients with colorectal cancer. Cancer Epidemiol, 38, 79-84.   DOI
16 Sui X, Xu Y, Yang J, et al (2014). Use of metformin alone is not associated with survival outcomes of colorectal cancer cell but AMPK activator AICAR sensitizes anticancer effect of 5-fluorouracil through AMPK activation. PLoS One, 9, 97781.   DOI
17 Trevisan M, Liu J, Muti P, et al (2001). Markers of insulin resistance and colorectal cancer mortality. Cancer Epidemiol Biomarkers Prev, 10, 937-41.
18 Tsilidis K, Capothanassi D, Allen N, et al (2014). Metformin does not affect cancer risk: a cohort study in the U.K. Clinical Practice Research Datalink analyzed like an intention-totreat trial. Diabetes Care, 37, 2522-32.   DOI
19 Huang HE, Yang YC, Wu JS, et al (2014). The relationship between different glycemic statuses and colon polyps in a Taiwanese population. J Gastroenterol, 49, 1145-51.   DOI
20 Inoue M, Tsugane S (2012). Insulin resistance and cancer: epidemiological evidence. Endocr Relat Cancer, 19, F1-8.   DOI
21 Jenkins P (2004). Acromegaly and cancer. Horm Res, 62, 108-15.   DOI
22 Kalaany N, Sabatini D (2009). Tumours with PI3K activation are resistant to dietary restriction. Nature, 458, 725-31.   DOI
23 Kanadiya M, Gohel T, Sanaka M, Thota P, Shubrook J (2013). Relationship between type-2 diabetes and use of metformin with risk of colorectal adenoma in an American population receiving colonoscopy. J Diabetes Complications, 27, 463-6.   DOI
24 Kaneko R, Nakazaki N, Tagawa T, et al (2014) A new index of abdominal obesity which effectively predicts risk of colon tumor development in female Japanese. Asian Pac J Cancer Prev, 15, 1005-10.   DOI
25 Khaw K, Wareham N, Bingham S, et al (2004). Preliminary communication: glycated hemoglobin, diabetes, and incident colorectal cancer in men and women: a prospective analysis from the European prospective investigation into cancer-Norfolk study. Cancer Epidemiol Biomarkers Prev, 13, 915-9.
26 Kim D (2012). [Obesity and gastrointestinal cancer-related factor]. Korean J Gastroenterol, 59, 8-15.   DOI
27 Larsson S, Wolk A (2007). Obesity and colon and rectal cancer risk: a meta-analysis of prospective studies. Am J Clin Nutr, 86, 556-65.   DOI
28 Lee D, Kim B, Lee J, et al (2012). The effect of metformin on responses to chemotherapy and survival in stage IV colorectal cancer with diabetes. Korean J Gastroenterol, 60, 355-61.   DOI
29 Wang X, Zhang Y (2014). Targeting mTOR network in colorectal cancer therapy. World J Gastroenterol, 20, 4178-88.   DOI
30 Vu HT, Ufere N, Yan Y, et al (2014). Diabetes mellitus increases risk for colorectal adenomas in younger patients. World J Gastroenterol, 20, 6946-52.   DOI
31 Warren R, Yuan H, Matli M, Ferrara N, Donner D (1996). Induction of vascular endothelial growth factor by insulinlike growth factor 1 in colorectal carcinoma. J Biol Chem, 271, 29483-8.   DOI
32 Williams A, Collard T, Perks C, et al (2000). Increased p53- dependent apoptosis by the insulin-like growth factor binding protein IGFBP-3 in human colonic adenoma-derived cells. Cancer Res, 60, 22-7.
33 Yun K, Chang Y, Jung H, et al (2013). Impact of body mass index on the risk of colorectal adenoma in a metabolically healthy population. Cancer Res, 73, 4020-7.   DOI
34 Zaafar D, Zaitone S & Moustafa Y (2014). Role of metformin in suppressing 1,2-dimethylhydrazine-induced colon cancer in diabetic and non-diabetic mice: effect on tumor angiogenesis and cell proliferation. PLoS One, 9, 100562.   DOI
35 Zaninotto P, Pierce M, Breeze E, De Oliveira C, Kumari M (2010). BMI and waist circumference as predictors of wellbeing in older adults: findings from the english longitudinal study of ageing. Obesity, 18, 1981-7.   DOI
36 Zhang P, Li H, Tan X, Chen L, Wang S (2013a). Association of metformin use with cancer incidence and mortality: a metaanalysis. Cancer Epidemiol, 37, 207-18.   DOI
37 Zhang Y, Guan M, Zheng Z, et al (2013b). Effects of metformin on CD133+ colorectal cancer cells in diabetic patients. PLoS
38 Mahmood K, Naeem M & Rahimnajjad N (2013). Metformin: the hidden chronicles of a magic drug. Eur J Intern Med, 24, 20-6.   DOI
39 Lega I, Shah P, Margel D, et al (2014). The effect of metformin on mortality following cancer among patients with diabetes. Cancer Epidemiol Biomarkers Prev, 23, 1974-84.   DOI
40 Li W, Wang Q, Liu X, et al (2015). Combined use of vitamin D3 and metformin exhibits synergistic chemopreventive effects on colorectal neoplasia in rats and mice. Cancer Prev Res, 8, 139-48.   DOI
41 Mei Z, Zhang Z, Liu C, et al (2014). Survival benefits of metformin for colorectal cancer patients with diabetes: a systematic review and meta-analysis. PLoS One, 9, 91818.   DOI
42 Mulholland H, Murray L, Cardwell C & Cantwell M (2009). Glycemic index, glycemic load, and risk of digestive tract neoplasms: a systematic review and meta-analysis. Am J Clin Nutr, 89, 568-76.   DOI
43 Na S & Myung S (2012). [Obesity and colorectal cancer]. Korean J Gastroenterol, 59, 16-26.   DOI
44 Ogden C, Carroll M, Curtin L, et al (2006). Prevalence of overweight and obesity in the United States, 1999-2004. JAMA, 295, 1549-55.   DOI
45 Pais R, Silaghi H, Silaghi A, Rusu M & Dumitrascu D (2009). Metabolic syndrome and risk of subsequent colorectal cancer. World J Gastroenterol, 15, 5141-8.   DOI
46 Rampal S, Yang MH, Sung J, et al (2014). Association between markers of glucose metabolism and risk of colorectal adenoma. Gastroenterol, 147, 78-87.   DOI
47 Renehan A, Roberts D, Dive C (2008). Obesity and cancer: pathophysiological and biological mechanisms. Arch Physiol Biochem, 114, 71-83.   DOI