Advertisement

Preclinical Models Relevant to Diet, Exercise, and Cancer Risk

  • R. James Barnard
  • William J. Aronson
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 166)

Abstract

Metabolic syndrome was initially described as an aggregation of risk factors for the development of coronary artery disease with insulin resistance and compensatory hyperinsulinemia as the underlying factor. In an earlier review, we suggested that hyperinsulinemia may also lead to prostate cancer (PCa), the most common male cancer in industrialized nations. Furthermore, we suggested that diet and exercise, known to be important in the development of insulin resistance, may also be important in the development of PCa. When we placed men from the United States on a low-fat diet and/or exercise program, serum levels of insulin, free testosterone, estradiol and insulin-like growth factor (IGF)-1 were reduced while sex hormone-binding globulin (SHBG) and insulin like growth factor binding protein (IGFBP)-1 were elevated. These in vivo serum changes directly impacted on androgen-dependent prostate cancer cell lines in vitro to reduce cell growth and induce apoptosis. The reduction in serum IGF-1 and increase in IGFBP-1 with diet and exercise appear to be the most significant, as these changes lead to an increase in tumor cell p53 protein and its down-stream effector p21, which are responsible for the reduction in cell growth and induced apoptosis. Preliminary results from a clinical study with men on “watchful waiting” indicate that the observed in vitro effects of diet and exercise on prostate cancer cell growth also occur in vivo.

Keywords

Prostate Cancer Benign Prostatic Hyperplasia Prostate Cancer Cell LNCaP Cell Prostate Cancer Risk 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Anderson DC (1974) Sex-hormone-binding globulin. Clin Endocrinol (Oxf) 3:69–96Google Scholar
  2. 2.
    Barnard RJ, Ugianskis EJ, Martin DA, Inkeles SB (1992) Role of diet and exercise in the management of hyperinsulinemia and associated atherosclerotic risk factors. Am J Cardiol 69:440–444PubMedCrossRefGoogle Scholar
  3. 3.
    Barnard RJ, Faria DJ, Menges JE, Martin DA (1993) Effects of a high-fat, sucrose diet on serum insulin and related atherosclerotic risk factors in rats. Atherosclerosis 100:229–236PubMedCrossRefGoogle Scholar
  4. 4.
    Barnard RJ, Wen SJ (1994) Exercise and diet in the prevention and control of the metabolic syndrome. Sports Med 18:218–228PubMedCrossRefGoogle Scholar
  5. 5.
    Barnard RJ, Roberts CK, Varon SM, Berger JJ (1998) Diet-induced insulin resistance precedes other aspects of the metabolic syndrome. J Appl Physiol 84:1311–1315PubMedGoogle Scholar
  6. 6.
    Barnard RJ, Aronson WJ, Tymchuk CN, Ngo TH (2002) Prostate cancer: another aspect of the insulin-resistance syndrome? Obes Rev 3: 303–308PubMedCrossRefGoogle Scholar
  7. 7.
    Barnard RJ, Ngo TH, Leung, P-S, Aronson WJ, Golding LA (2003) A low-fat diet and/ or strenuous exercise alters the IGF axis in vivo and reduces prostate tumor cell growth in vitro. Prostate 56:201–206PubMedCrossRefGoogle Scholar
  8. 8.
    Castagnetta LA, Miceli MD, Sorci CM, Pfeffer U, Farruggio R, Oliveri G, Calabrò M, Carruba G (1995) Growth of LNCaP human prostate cancer cells is stimulated by estradiol via its own receptor. Endocrinology 136:2309–2319PubMedCrossRefGoogle Scholar
  9. 9.
    Chan JM, Stampfer MJ, Giovannucci E, Gann PH, Ma J, Wilkinson P, Hennekens CH, Pollak M (1998) Plasma insulin-like growth factor-1 and prostate cancer risk: a prospective study. Science 279:563–566PubMedCrossRefGoogle Scholar
  10. 10.
    Chokkalingam AP, Pollak M, Fillmore CM, Gao YT, Deng J, Sesterhenn IA, Mostofi FK, Fear TR, Madigan MP, Zeigler RG, Fraumeni JF Jr, Hsing AW (2001) Insulin-like growth factors and prostate caner: a population-based case-control study in China. Cancer Epidemiol Biomarkers Prev 10:421–427PubMedGoogle Scholar
  11. 11.
    Chokkalingam AP, Gao Y-T, Deng J, Stanczyk FZ, Sesterhenn IA, Mostofi FK, Fraumeni JF Jr, Hsing AW (2002) Insulin-like growth factors and risk of benign prostatic hyperplasia. Prostate 52: 98–105PubMedCrossRefGoogle Scholar
  12. 12.
    Coffey DS, Pienta KJ (1987) New concepts in studying control of normal growth of the prostate. Prog Clin Biol Res 239:1–73PubMedGoogle Scholar
  13. 13.
    Cohen P, Peehl DM, Rosenfeld RG (1994) The IGF axis in the prostate. Horm Metab Res 26:81–84PubMedCrossRefGoogle Scholar
  14. 14.
    DeFronzo RA, Ferrannini E (1991) Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia and atherosclerotic cardiovascular disease. Diabetes Care 14:173–194PubMedGoogle Scholar
  15. 15.
    Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001) Executive summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 285:2486–2497Google Scholar
  16. 16.
    Gann PH, Hennekens CH, Ma J, Longcope C, Stampfer MJ (1996) Prospective study of sex hormone levels and risk of prostate cancer. J Natl Cancer Inst 88:1118–1126PubMedGoogle Scholar
  17. 17.
    Gurumurthy S, Vasudevan KM, Rangnekar VM (2001) Regulation of apoptosis in prostate cancer. Cancer Metastasis Rev 20:225–243PubMedCrossRefGoogle Scholar
  18. 18.
    Haffner SM, Valdez RA, Hazuda HP, Mitchell BD, Morales PA, Stern MP (1992) Prospective analysis of the insulin-resistance syndrome (syndrome X). Diabetes 41:715–722PubMedGoogle Scholar
  19. 19.
    Hammarsten J, Högstedt B, Holthuis N, Mellström D (1998) Components of the metabolic syndrome—risk factors for the development of benign prostatic hyperplasia. Prostate Cancer Prostatic Dis 1:157–162PubMedCrossRefGoogle Scholar
  20. 20.
    Harman SM, Metter EJ, Blackman MR, Landis PK, Carter HB (2000) Serum levels of insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-3 and prostate-specific antigen as predictors of clinical prostate cancer. J Clin Endocrinol Metab 85:4258–4265PubMedCrossRefGoogle Scholar
  21. 21.
    Heron-Milhavet L, LeRoith D (2002) IGF-1 induces MDM 2-dependent degradation of p53 via the p38 MAP kinase pathway in response to DNA damage. J Biol Chem 277:15600–15606.PubMedCrossRefGoogle Scholar
  22. 22.
    Hsing AW, Chua SJr, Gao YT, Gentzschein E, Chang L, Deng J, Stanczyk FZ (2001) Prostate cancer risk and serum levels of insulin and leptin: a population-based study. J Natl Cancer Inst 93:783–789PubMedCrossRefGoogle Scholar
  23. 23.
    Hsing AW, Gao YT, Chua S Jr, Deng J, Stanczyk FZ (2003) Insulin resistance and prostate cancer risk. J Natl Cancer Inst 95: 1086–1087Google Scholar
  24. 24.
    Kaplan NM (1989) The deadly quartet. Upper-body obesity, glucose intolerance, hypertriglyceridemia and hypertension. Arch Intern Med 149:1514–1520PubMedGoogle Scholar
  25. 25.
    Katsuki A, Sumida Y, Murashima S, Fujii M, Ito K, Tsuchihashi K, Murata K, Yano Y, Shima T (1996) Acute and chronic regulation of serum sex hormone-binding globulin levels by plasma insulin concentrations in male non-insulin-dependent diabetes mellitus patients. J Clin Endocrinol Metab 81:2515–2519PubMedCrossRefGoogle Scholar
  26. 26.
    King GL, Kahn CR (1981) Non-parallel evolution of metabolic and growth-promoting functions of insulin. Nature 292:644–646PubMedGoogle Scholar
  27. 27.
    Lee IM, Sesso HD, Chen JJ, Pattenbarger RS Jr (2001) Does physical activity play a role in the prevention of prostate cancer? Epidemiol Rev 23:132–137PubMedGoogle Scholar
  28. 28.
    Lehrer S, Diamond EJ, Stagger S, Stone NN, Stock RG (2002) Increased serum insulin associated with increased risk of prostate cancer recurrence. Prostate 50:1–3PubMedCrossRefGoogle Scholar
  29. 29.
    Leung P-S, Aronson WJ, Ngo TH, Golding LA, Barnard RJ (2004) Exercise alters the IGF axis in vivo and increases p53 protein in prostate tumor cells in vitro. J Appl Physiol 96:450–454PubMedCrossRefGoogle Scholar
  30. 30.
    LeRoith D, Werner H, Beitner-Johnson D, Roberts CT Jr (1995) Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocr Rev 16:143–163PubMedCrossRefGoogle Scholar
  31. 31.
    LeRoith D, Roberts CT Jr (2003) The insulin-like growth factor system and cancer. Cancer Lett 195:127–137PubMedGoogle Scholar
  32. 32.
    Mantzoros CS, Tzonou A, Signorello LB, Stampfer M, Trichopoulos D, Adami HO (1997) Insulin-like growth factor-I in relation to prostate cancer and benign prostatic hyperplasia. Br J Cancer 76:1115–1118PubMedGoogle Scholar
  33. 33.
    Ngo TH, Barnard RJ, Tymchuk CN, Cohen P, Aronson WJ (2002) Effect of diet and exercise on serum insulin, IGF-I, and IGFBP-1 levels and growth of LNCaP cells in vitro (United States). Cancer Causes Control 13: 929–935PubMedCrossRefGoogle Scholar
  34. 34.
    Ngo TH, Barnard RJ, Leung P-S, Cohen P, Aronson WJ (2003) Insulin-like growth factor I (IGF-I) and IGF binding protein-1 modulate prostate cancer cell growth and apoptosis: possible mediators for the effects of diet and exercise on cancer cell survival. Endocrinology 144: 2319–2324PubMedCrossRefGoogle Scholar
  35. 35.
    Ornish D, Lee KL, Fair WR, Pettengill EB, Carroll PR (2001) Dietary trial in prostate cancer: early experience and implications for clinical trial design. Urology 57:200–201PubMedCrossRefGoogle Scholar
  36. 37.
    Pasquali R, Casimirri F, De Iasio R, Mesini P, Boschi S, Chierici R, Flamia R, Biscotti M, Vicennati V (1995) Insulin regulates testosterone and sex hormone-binding globulin concentrations in adult normal-weight and obese men. J Clin Endocrinol Metab 80:654–658PubMedGoogle Scholar
  37. 38.
    Platz EA, Kawachi I, Rimm EB, Colditz GA, Stampfer MJ, Willett WC, Giovannucci E (1998) Physical activity and benign prostatic hyperplasia. Arch Intern Med 158:2349–2356PubMedCrossRefGoogle Scholar
  38. 39.
    Plymate SR, Matej LA, Jones RE, Friedl KE (1989) Inhibition of sex hormone-binding globulin in the human hepatoma (HepG2) cell line by insulin and prolactin. J Clin Endocrinol Metab 67:460–464Google Scholar
  39. 40.
    Plymate SR, Hoop RC, Jones RE, Matej LA (1990) Regulation of sex hormone-binding globulin production by growth factors. Metabolism 39: 967–970PubMedCrossRefGoogle Scholar
  40. 41.
    Polychronakos C, Janthly U, Lehoux JG, Koutsilieris M (1991) Mitogenic effects of insulin and insulin-like growth factors on PA-III rat prostate adenocarcinoma cells: characterization of the receptors involved. Prostate 19:313–321PubMedGoogle Scholar
  41. 42.
    Reaven GM (1988) Banting Lecture 1988. Role of insulin resistance in human disease. Diabetes 37:1595–1607PubMedGoogle Scholar
  42. 43.
    Reed MJ, Cheng RW, Simmonds M, Richmond W, James VHT (1987) Dietary lipids: an additional regulator of plasma levels of sex hormone-binding globulin. J Clin Endocrinol Metab 64:1083–1085PubMedCrossRefGoogle Scholar
  43. 44.
    Ritchie CK, Andrew, LR, Thomas KG, Tindall DJ, Fitzpatrick LA (1997) The effects of growth factor, associated with osteoblasts on prostate carcinoma proliferation and chemotaxis: implications for the development of metastatic disease. Endocrinology 138:1145–1150PubMedCrossRefGoogle Scholar
  44. 45.
    Roberts CK, Vaziri ND, Liang KH, Barnard RJ (2001) Reversibility of chronic experimental syndrome X by diet modification. Hypertension 37:1323–1328PubMedGoogle Scholar
  45. 46.
    Rokhlin W, Gudkov AV, Kwek S, Glover RA, Gewies AS, Cohen MB (2000) p53 is involved in tumor necrosis factor-alpha-induced apoptosis in the human prostatic carcinoma cell line LNCaP.Oncogene 19:1959–1968PubMedCrossRefGoogle Scholar
  46. 47.
    Rosenthal MB, Barnard RJ, Rose DP, Inkeles S, Hall J, Pritikin N (1985) Effect of a high-complex-carbohydrate, low-fat, low-cholesterol diet on serum lipids and estradiol. Am J Med 78:23–27PubMedCrossRefGoogle Scholar
  47. 48.
    Stattin P, Bylund A, Rinaldi S, Biessy C, Dèchaud H, Stenman U-H, Egevad L, Hallmans G, Kaaks R (2000) Plasma insulin-like growth fator-1, insulin-like growth factor-binding proteins, and prostate cancer risk: a prospective study. J Natl Cancer Inst 92:1910–1917PubMedCrossRefGoogle Scholar
  48. 49.
    Strain GK, Zumoff B, Rosner W, Pi-Sunyer X (1994) The relationship between serum levels of insulin and sex hormone-binding globulin in men: the effect of weight loss. J Clin Endocrinol Metab 79:1173–1176PubMedCrossRefGoogle Scholar
  49. 50.
    Thissen J-P, Ketelslegers J-M, Underwood LE (1994) Nutritional regulation of the insulin-like growth factors. Endocr Rev 15: 80–101PubMedCrossRefGoogle Scholar
  50. 51.
    Thune I, Furberg AS (2001) Physical activity and cancer risk: dose-response and cancer, all sites and site-specific. Med Sci Sports Exerc 33:S530–S550PubMedGoogle Scholar
  51. 52.
    Tymchuk CN, Tessler SB, Aronson WJ, Barnard RJ (1998) Effects of diet and exercise on insulin, sex hormone-binding globulin, and prostate-specific antigen. Nutr Cancer 31:127–131PubMedCrossRefGoogle Scholar
  52. 53.
    Tymchuk CN, Tessler SB, Barnard RJ (2000) Changes in sex hormone-binding globulin, insulin, and serum lipids in postmenopausal women on a low-fat, high-fiber diet combined with exercise. Nutr Cancer 38: 158–162PubMedCrossRefGoogle Scholar
  53. 54.
    Tymchuk CN, Barnard RJ, Heber D, Aronson WJ (2001) Evidence of an inhibitory effect of diet and exercise on prostate cancer cell growth. J Urol 166:1185–1189PubMedGoogle Scholar
  54. 55.
    Tymchuk CN, Barnard RJ, Ngo TH, Aronson WJ (2002) The role of testosterone, estradiol, and insulin in diet and exercise-induced reductions in prostate cancer cell growth in vitro. Nutr Cancer 42:112–116PubMedGoogle Scholar
  55. 56.
    Wang Y, Corr JG, Thaler HT, Fair WR, Heston WDW (1995) Decreased growth of established human prostate LNCaP tumors in nude mice fed a low-fat diet. J Natl Cancer Inst 87:1456–1462PubMedGoogle Scholar
  56. 57.
    Wolk A, Mantzoros CS, Andersson SO, Bergstrom R, Signorello LB, Lagiou P, Adami HO, Trichopoulos D (1998) Insulin-like growth factor-1 and prostate cancer risk: a population-based, case-control study. J Natl Cancer Inst 90:911–915PubMedCrossRefGoogle Scholar
  57. 58.
    World Health Organization (1999) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus. World Health Organization, GenevaGoogle Scholar
  58. 59.
    Yarak S, Liu JL, Stannard B, Butter A, Accili D, Sauer B, LeRoith D (1999) Normal growth and development in the absence of hepatic insulin-like growth factor I. Proc Natl Acad Sci USA 96:7324–7329Google Scholar
  59. 60.
    Yu H, Rohan T (2000) Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst 92: 1472–1489PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • R. James Barnard
    • 1
  • William J. Aronson
    • 1
  1. 1.Departments of Physiological Science and UrologyUniversity of California, Los AngelesLos AngelesUSA

Personalised recommendations