Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Use of Oral Antidiabetic Drugs (Metformin and Pioglitazone) in Diabetic Patients with Breast Cancer: How Does It Effect on Serum Hif-1 Alpha and 8Ohdg Levels?

  • Ece, Harman (Department of Endocrinology and Metabolism Disease, Katip Celebi University, Izmir Ataturk Training and Research Hospital) ;
  • Cigdem, Erten (Department of Medical Oncology, Katip Celebi University, Izmir Ataturk Training and Research Hospital) ;
  • Yuksel, Kucukzeybek (Department of Medical Oncology, Katip Celebi University, Izmir Ataturk Training and Research Hospital) ;
  • Ahmet, Dirican (Department of Medical Oncology, Katip Celebi University, Izmir Ataturk Training and Research Hospital) ;
  • Hakan, Er (Department of Microbiology, Katip Celebi University, Izmir Ataturk Training and Research Hospital) ;
  • Oktay, Tarhan Mustafa (Department of Medical Oncology, Katip Celebi University, Izmir Ataturk Training and Research Hospital)
  • Published : 2012.10.31
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Abstract

Objective: The aim was to investigate indicators related to DNA damage and cancer pathogenesis in Type II diabetes cases with breast cancer. It was planned to evaluate the relationship between these markers with oral antidiabetic drugs. Research Design and Methods: Fourty patients and 10 healthy individuals were included in the study. HIF-$1{\alpha}$ and 8-OHdG are examined in blood samples taken from these individuals with an ELISA Kit. Statistical analysis of data was performed with 95% confidence using Windows package program SPSS 15.0. Results: HIF-$1{\alpha}$ parameters were found to be meaningfully higher in the patient group than the controls in both pretreatment and posttreatment periods (p<0.05). No significant differences in terms of 8-OHdG between patients and controls. However, posttreatment serum HIF-$1{\alpha}$ ve 8-OHdG levels was found lower than pretreatment levels in patients receiving metformin, but not with pioglitazone. Conversely, serum 8-OHdG levels decreased significantly in these patients. When patients were evaluated according to the treatment groups (pioglitazone vs. metfformin) no significant differences in terms of serum HIF-$1{\alpha}$ and 8-OHdG levels between treatment groups. Conclusions: HIF-$1{\alpha}$ levels decreased significantly in the patient group receiving metformin. However, there was no significant difference in terms of HIF-$1{\alpha}$ levels in the patients receiving pioglitazone.

Keywords

References

  1. Abbasi F, Chu JW, McLaughlin T, et al (2004). Effect of metformin treatment on multiple cardiovascular disease risk factors in patients with type 2 diabetes mellitus. Metabolism, 53, 159-64. https://doi.org/10.1016/j.metabol.2003.07.020
  2. ADA Guidelines (2012). Executive Summary: Standarts of Medical Care in Diabetes. Diabetes Care v, 35, PAGE?.
  3. Al-Aubaidy HA, Jelinek HF (2010). 8-Hydroxy-2-deoxyguanosine identifies oxidative DNA damage in a rural prediabetes cohort. Redox Rep, 15, 155-60. https://doi.org/10.1179/174329210X12650506623681
  4. Anderson D, Yu TW, Wright J, et al (1998). An examination of DNA strand breakage in the comet assay and antioxidant capacity in diabetic patients. Mutat Res, 398, 151-6. https://doi.org/10.1016/S0027-5107(97)00271-6
  5. Arif M, Islam MR, Hassan F, et al (2010). DNA damage and plasma antioxidant indices in Bangladeshi type 2 diabetic patients. Diabetes Metab, 36, 51-7. https://doi.org/10.1016/j.diabet.2009.05.007
  6. Assiamira Ferrara, James DL, Charles PQ, et al (2011). Cohort study of pioglitazone and cancer incidence in patients with diabetes. Diabetes Care, 34, 923-9. https://doi.org/10.2337/dc10-1067
  7. Bailey CJ, Turner RC (1996). Metformin N Engl J Med, 334, 574-9. https://doi.org/10.1056/NEJM199602293340906
  8. Bast A, Wolf G, Oberbäumer I, et al (2002). Oxidative and nitrosative stress induces peroxiredoxins in pancreatic beta cells. Diabetologia, 45, 867-76. https://doi.org/10.1007/s00125-002-0846-1
  9. Bento CF, Pereira P (2011). Regulation of hypoxia-inducible factor 1 and the loss of the cellular response to hypoxia in diabetes. Diabetologia, 54, 1946-56. https://doi.org/10.1007/s00125-011-2191-8
  10. Bhatia S, Shukla R, Venkata Madhu, et al (2003). Antioxidant status, lipid peroxidation and nitric oxide end products in patients of type 2 diabetes mellitus with nephropathy. Clin Biochem, 36, 557-62. https://doi.org/10.1016/S0009-9120(03)00094-8
  11. Bonnefont-Rousselot D, Bastard JP, Jaudon MC, et al (2000). Consequences of the diabetic status on the oxidant/antioxidant balance. Diabetes Metab, 26, 163-76.
  12. Bos R, Zhong H, Hanrahan CF, et al (2002). Levels of hypoxiainducible factor 1 alpha during breast carcinogenesis. J Natl Cancer Res, 93, 309-14.
  13. Changtao J, Aijuan Q, Tsutomu M, et al (2011). Disruption of Hypoxia-inducible factor 1 in adipocytes improves insülin sensitivity and decreases adiposity in high-fat diet-fed mice. Diabetes, 60, 2484-95. https://doi.org/10.2337/db11-0174
  14. Currie CJ, Poole CD, Gale EAM (2009). The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. JOURNAL?, 52, 1766-77.
  15. Del Giudice ME, Fantus IG, Ezzat S, et al (1998). Insulin and related factors in premenopausal breast cancer risk. Breast Cancer Res Treat, 47, 111-20. https://doi.org/10.1023/A:1005831013718
  16. Dormandy JA, Charbonnel B, Eckland DJ, et al (2005). PROactive investigators. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet, 366, 1279-89. https://doi.org/10.1016/S0140-6736(05)67528-9
  17. Elstner E, Müller C, Koshizuka K, et al (1998). Ligands for peroxisome proliferator-activated receptorgamma and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. Proc Natl Acad Sci USA, 95, 8806-11. https://doi.org/10.1073/pnas.95.15.8806
  18. European Medicines Agency, Committee for medicinal products for human use. (21 July 2011). Pioglitazon Accord, Summary of opinion (initial authorisation), website: www.ema.europa.eu ; e-mail: info@ema.europa.eu
  19. Evans JM, Donnelly LA, Emslie-Smith AM, et al (2005). Metformin and reduced risk of cancer in diabetic patients. BMJ, 330, 1304-5. https://doi.org/10.1136/bmj.38415.708634.F7
  20. Feng Z, Zhang H, Levine AJ, et al (2005). The coordinate regulation of the p53 and mTOR pathways in cells. Proc Natl Acad Sci USA, 102, 8204-9. https://doi.org/10.1073/pnas.0502857102
  21. Food and Drug Administration (2010). FDA drug safety communication: ongoing safety review of actos (pioglitazone) and potential increased risk of bladder cancer after two years expose (Internet),
  22. Fridlyand LE, Philipson LH (2006). Reactive species and early manifestation of insulin resistance in type 2 diabetes. Diabetes Obes Metab, 8, 136-45. https://doi.org/10.1111/j.1463-1326.2005.00496.x
  23. Gapstur SM, Gann PH, Colangelo LA, et al (2001). Postload plasma glucose concentration and 27-year prostate cancer mortality (United States). Cancer Causes Control, 12, 763-72. https://doi.org/10.1023/A:1011279907108
  24. Giovannucci E (1995). Insulin and colon cancer. Cancer Causes Control, 6, 164-79. https://doi.org/10.1007/BF00052777
  25. Govindarajan R, Ratnasinghe L, Simmons DL (2007). Thiazolidinediones and the risk of lung, prostate, and colon cancer in patients with diabetes. J Clin Oncol, 25, 1476-81. https://doi.org/10.1200/JCO.2006.07.2777
  26. Gunton JE, Kulkarni RN, Yim S, et al (2005). Loss of ARNT/HIF1${\beta}$ mediates altered gene expression and pancreatic-islet dysfunction in human type 2 diabetes. Cell, 122, 337-49. https://doi.org/10.1016/j.cell.2005.05.027
  27. Hannon-Fletcher MP, O' Kane MJ, Moles KW, et al (2000). Levels of peripheral blood cell DNA damage in insülin dependent diabetes mellitus human subjects. Mutat Res, 460, 53-60. https://doi.org/10.1016/S0921-8777(00)00013-6
  28. Hardie DG, Hamley SA (2001). AMP-activated protein kinase: the energy charge hypothesis revisited. Bioessays, 23, 1112-9. https://doi.org/10.1002/bies.10009
  29. Hawley SA, Gadalla AE, Olsen GS, et al (2002). The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism. Diabetes, 51, 2420-5. https://doi.org/10.2337/diabetes.51.8.2420
  30. Hay N, Sonenberg N (2004). Upstream and downstream of mTOR. Genes Dev, 18, 1926-45. https://doi.org/10.1101/gad.1212704
  31. James D Lewis, Assiamira Ferrara, Tiffany Peng, et al (2011). Risk of bladder cancer among diabetiv patients treated with pioglitazone. Diabetes Care, 34, 916-22. https://doi.org/10.2337/dc10-1068
  32. Kemp BE, Stapleton D, Campbell DJ (2003). AMP-activated protein kinase, super metabolic regulator. Biochem Soc Trans, 31:162-8. ndocrine-Related Cancer, 13, 739-49.
  33. Kimbro K S, Simons JW (2006). Hypoxia-inducible factor-1 in human breast and prostate cancer. Endocrine-Related Cancer, 13, 739-49. https://doi.org/10.1677/erc.1.00728
  34. Koro C, Barrett S, Qizilbash N (2007). Cancer risks in thiazolidinedione users compared to other anti-diabetic agents. Pharmaco-epidemiol Drug Saf, 16, 485492.
  35. Kubota T, Koshizuka K, Williamson EA, et al (1998) Ligand for peroxisome proliferator-activated receptor gamma (Troglitazone) has potent antitumor effect against human prostat cancer both in vitro and in vivo. Cancer Res, 58, 3344-52.
  36. Liang Z, Wu T, Lou H, et al (2004). Inhibition of breast cancer metastasis by selective synthetic polypeptide against CXCR4. Cancer Res, 64, 4302-8. https://doi.org/10.1158/0008-5472.CAN-03-3958
  37. Lim JH, Lee ES, You HJ, et al (2004). Ras-dependent induction of HIF-1 alpha785 via the Raf/MEK/ERK pathway: a novel mechanism of Ras-mediated tumor promotion. Oncogene, 23, 9427-31. https://doi.org/10.1038/sj.onc.1208003
  38. Liu H, Zang C, Fenner MH et al (2003). PPARgamma ligands and ATRA inhibit the invasion of human breast cancer cells in vitro. Breast Cancer Res Treat, 79, 63-77. https://doi.org/10.1023/A:1023366117157
  39. Luiz Gustavo Oliveira Brito, Viviane Fernandes Schiavon, Jurandyr Moreira da Andrade, et al (2011). Expression of Hypoxia-inducible factor 1-α and vascular endothelial growth factor-C in locally advanced breast cancer patients. Clin Sci, 66, 1313-9.
  40. Martinez-Outschoorn UE, Balliet RM, Rivadeneira DB, et al (2010). Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: A new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells. Cell Cycle, 9, 3256-76. https://doi.org/10.4161/cc.9.16.12553
  41. Mueller E, Sarraf P, Tontonoz P, et al (1998). Terminal differentiation of human breast cancer through PPAR gamma. Mol Cell, 1, 465-70. https://doi.org/10.1016/S1097-2765(00)80047-7
  42. Musarrat J, Arezina-Wilson J, Wani AA (1996). Prognostic and aetiological relevance of 8-hydroxyguanosine in human breast carcinogenesis. Eur J Cancer, 32A, 1209-14.
  43. Nathan DM, Buse JB, Davidson MB, et al (2009). American Diabetes Association; European Association for Study of Diabetes. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care, 32, 193-203. https://doi.org/10.2337/dc08-9025
  44. Paolo Vigneri, Francesco Frasca, Laura Sciacca, et al (2009). Diabetes and cancer. Endocrine-Related Cancer, 16, 1103-23. https://doi.org/10.1677/ERC-09-0087
  45. Rathmann W, Giani G (2004). Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care, 27, 2568-9. https://doi.org/10.2337/diacare.27.10.2568
  46. Rosen P, Nawroth PP, King G, et al (2001). The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a Congress Series sponsored by UNESCO-MCBN, the American Diabetes Association and the German Diabetes Society. Diabetes Metab Res Rev, 17, 189-212. https://doi.org/10.1002/dmrr.196
  47. Rubenstrunk A, Hanf R, Hum DW, et al (2007). Safety issues and prospects for future generations of PPAR modulators. Biochim Biophys Acta, 1771, 1065-81. https://doi.org/10.1016/j.bbalip.2007.02.003
  48. Rahimi R, Nikfar S, Larijani B, et al (2005). A review on role of antioxidants in the management of diabetes and its complications. Biomed Pharmacother. 59, 365-73. https://doi.org/10.1016/j.biopha.2005.07.002
  49. Rikio Y, Masahide M, Yoshihiro S, et al (2003). Expression of peroxisome proliferator activated receptors (PPARs) in human urinary bladder carcinoma and growth inhibition by its agonists. Int J Cancer, 104, 597-602. https://doi.org/10.1002/ijc.10980
  50. Sabatini DM (2006). mTOR and cancer: insights into a complex relationship. Nat Rev Cancer, 6, 729-34 https://doi.org/10.1038/nrc1974
  51. Samuni Y, Cook JA, Choudhuri R, et al (2010). Inhibition of adipogenesis by Tempol in 3T3-L1 cells. Free Radic Biol Med, 49, 667-73. https://doi.org/10.1016/j.freeradbiomed.2010.05.028
  52. Semenza GL (2010). Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene, 29, 625-34. https://doi.org/10.1038/onc.2009.441
  53. Suzuki S, Arnold LL, Pennigton KL, et al (2010). Effects of pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, on the urine and urothelium of the rat. Toxicol Sci, 113, 349-57. https://doi.org/10.1093/toxsci/kfp256
  54. Talks KL, Turley H, Gatter KC, et al (2000). The expression and distribution of the hypoxia-inducible factors HIF-1 alpha and HIF-2 alpha in normal human tissues, cancers, and tumor-associated macrophages. Am J Pathol, 157, 411-21. https://doi.org/10.1016/S0002-9440(10)64554-3
  55. UK Prospective Diabetes Study (UKPDS) Group (1998). Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet, 352, 854-65. https://doi.org/10.1016/S0140-6736(98)07037-8
  56. Van Diest PJ, Vleugel Mm, Van der Wall E (2005). Expression of HIF-1 alpha in human tumours. J Clin Pathol, 58, 335-6.
  57. Van Dyke K, Jabbour N, Hoeldtke R, et al (2010). Oxidative/nitrosative stresses trigger I diabetes: preventable in streptozotocin rats and detectable in human disease. Ann N Y Acad Sci, 1203, 138-45. https://doi.org/10.1111/j.1749-6632.2010.05563.x
  58. Wu LL, Chiou CC, Chang PY, et al (2004). Urinary 8-OHdG: a marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetics. Clin ChimActa, 339, 1-9. https://doi.org/10.1016/j.cccn.2003.09.010
  59. Wullschleger S, Loewith R, Hall MN (2006). TOR signaling in growth and metabolism. Cell, 124, 471-84. https://doi.org/10.1016/j.cell.2006.01.016
  60. Zheng F, Lu W, Jia C, et al (2010). Relationships between glucose excursion and the activation of oxidative stress in patients with newly diagnosed type 2 diabetes or impaired glucose regulation. Endocrine, 37, 201-8. https://doi.org/10.1007/s12020-009-9296-6
  61. Zong H, De Marzo AM, Laughner E, et al (1999). Overexpression of hypoxia-inducible factor1 alpha in common human cancers and their metastases. Cancer Res, 59, 5830-5.

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