Cancer Causes & Control

, Volume 13, Issue 10, pp 929–935 | Cite as

Effect of diet and exercise on serum insulin, IGF-I, and IGFBP-1 levels and growth of LNCaP cells in vitro (United States)

  • Tung H. Ngo
  • R. James Barnard
  • Christopher N. Tymchuk
  • Pinchas Cohen
  • William J. Aronson

Abstract

Objective: Accumulating evidence indicates that prostate cancer is associated with high levels of serum IGF-I. This study was conducted to determine whether a low-fat diet and exercise (DE) intervention may modulate the IGF axis and reduce prostate cancer cell growth in vitro. Methods: Fasting serum was obtained from 14 men (age 60 ± 3 years) participating in an 11-day DE program and from eight similarly aged men who had followed the DE program for 14.2 ± 1.7 years (long-term). Insulin, IGF-I, IGFBP-1, and IGFBP-3 were measured by ELISA, and serum was used to stimulate LNCaP cell growth in vitro. Results: Serum IGF-I levels decreased by 20% while IGFBP-1 increased by 53% after 11-day DE. In the long-term group, IGF-I was 55% lower, while IGFBP-1 was 150% higher relative to baseline. Serum insulin decreased by 25% after 11-day DE and was 68% lower in the long-term group, relative to baseline. No changes in serum IGFBP-3 were observed. Serum-stimulated LNCaP cell growth was reduced by 30% in post-11-day serum and by 44% in long-term serum relative to baseline. LNCaP cells incubated with post-DE serum showed increased apoptosis/necrosis, compared to baseline. Conclusions: A low-fat diet and exercise intervention induces in-vivo changes in the circulating IGF axis and is associated with reduced growth and enhanced apoptosis/necrosis of LNCaP tumor cells in vitro.

apoptosis dietary fat IGF-I axis physical activity prostate cancer 

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References

  1. 1.
    Giovannucci E, Rimm EB, Colditz GA, et al. (1993) A prospective study of dietary fat and risk of prostate cancer. J Natl Cancer Inst 85: 1571–1579.Google Scholar
  2. 2.
    Griffiths K, Boyle P (1995) Diet and prostate disease. Eur Urol Today 5: 9.Google Scholar
  3. 3.
    Haenszel W, Kurihara M (1968) Studies of Japanese migrants. I. Mortality from cancer and other diseases among Japanese in the United States. J Natl Cancer Inst 40: 43–68.Google Scholar
  4. 4.
    Whittemore AS, Kolonel LN, Wu AH, et al. (1995) Prostate cancer in relation to diet, physical activity, and body size in blacks, whites, and Asians in the United States and Canada. J Natl Cancer Inst 87: 652–661.Google Scholar
  5. 5.
    Fradet Y, Meyer F, Bairati I, Shadmani R, Moore L (1999) Dietary fat and prostate cancer progression and survival. Eur Urol 35: 388–391.Google Scholar
  6. 6.
    Wang Y, Corr JG, Thaler HT, Tao Y, Fair WR, Heston WD (1995) Decreased growth of established human prostate LNCaP tumors in nude mice fed a low-fat diet. J Natl Cancer Inst 87: 1456–1462.Google Scholar
  7. 7.
    Kondo Y, Homma Y, Aso Y, Kakizoe T (1994) Promotional effect of two-generation exposure to a high-fat diet on prostate carcinogenesis in ACI/Seg rats. Cancer Res 54: 6129–6132.Google Scholar
  8. 8.
    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: 1185–1189.Google Scholar
  9. 9.
    LeRoith D, Werner H, Beitner-Johnson D, Roberts CT Jr (1995) Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocrinol Rev 16: 143–163.Google Scholar
  10. 10.
    Chan JM, Stampfer MJ, Giovannucci EL (1998) What causes prostate cancer? A brief summary of the epidemiology. Semin Cancer Biol 8: 263–273.Google Scholar
  11. 11.
    Ritchie CK, Andrews LR, Thomas KG, Tindall DJ, Fitzpatrick LA (1997) The effects of growth factors associated with osteoblasts on prostate carcinoma proliferation and chemotaxis: implications for the development of metastatic disease. Endocrinology 138: 1145–1150.Google Scholar
  12. 12.
    Iwamura M, Sluss PM, Casamento JB, Cockett AT (1993) Insulinlike growth factor I: action and receptor characterization in human prostate cancer cell lines. Prostate 22: 243–252.Google Scholar
  13. 13.
    Wolk A, Mantzoros CS, Andersson SO, et al. (1998) Insulin-like growth factor 1 and prostate cancer risk: a population-based, case-control study. J Natl Cancer Inst 90: 911–915.Google Scholar
  14. 14.
    Mantzoros CS, Tzonou A, Signorello LB, Stampfer M, Trichopoulos D, Adami HO (1997) Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasia. Br J Cancer 76: 1115–1118.Google Scholar
  15. 15.
    Stattin P, Bylund A, Rinaldi S, et al. (2000) Plasma insulin-like growth factor-I, insulin-like growth factor-binding proteins, and prostate cancer risk: a prospective study. J Natl Cancer Inst 92: 1910–1917. 934 T.H. Ngo et al.Google Scholar
  16. 16.
    Chan JM, Stampfer MJ, Giovannucci E, et al. (1998) Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 279: 563–566.Google Scholar
  17. 17.
    Cohen P, Peehl DM, Rosenfeld RG (1994) The IGF axis in the prostate. Horm Metab Res 26: 81–84.Google Scholar
  18. 18.
    Collett-Solberg PF, Cohen P (1996) The role of the insulinlike growth factor binding proteins and the IGFBP proteases in modulating IGF action. Endocrinol Metab Clin N Am 25: 591–614.Google Scholar
  19. 19.
    Ferry RJ Jr, Katz LE, Grimberg A, Cohen P, Weinzimer SA (1999) Cellular actions of insulin-like growth factor binding proteins. Horm Metab Res 31: 192–202.Google Scholar
  20. 20.
    Katz LEL, Rosenfeld RG, Cohen P (1995) Clinical significance of insulin-like growth factor binding proteins (IGFBPs). Endocrinologist 5: 36–43.Google Scholar
  21. 21.
    Conover CA, Lee PD, Kanaley JA, Clarkson JT, Jensen MD (1992) Insulin regulation of insulin-like growth factor binding protein-1 in obese and nonobese humans. J Clin Endocrinol Metab 74: 1355–1360.Google Scholar
  22. 22.
    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: 127–131.Google Scholar
  23. 23.
    Yu H, Rohan T (2000) Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst 92: 1472–1489.Google Scholar
  24. 24.
    Underwood LE, Thissen JP, Lemozy S, Ketelslegers JM, Clemmons DR (1994) Hormonal and nutritional regulation of IGF-I and its binding proteins. Horm Res 42: 145–151.Google Scholar
  25. 25.
    Smith WJ, Underwood LE, Clemmons DR (1995) Effects of caloric or protein restriction on insulin-like growth factor-I (IGFI) and IGF-binding proteins in children and adults. J Clin Endocrinol Metab 80: 443–449.Google Scholar
  26. 26.
    Rosenthal MB, Barnard RJ, Rose DP, Inkeles S, Hall J, Pritikin N (1985) Effects of a high-complex-carbohydrate, low-fat, lowcholesterol diet on levels of serum lipids and estradiol. Am J Med 78: 23–27.Google Scholar
  27. 27.
    Tymchuk CN, Barnard RJ, Ngo TH, Aronson WJ (2002) The role of testosterone, estradiol, and insulin in diet and exercise-induced reductions in serum-stimulated prostate cancer cell growth in vitro. Nutr Cancer (In Press).Google Scholar
  28. 28.
    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: 440–444.Google Scholar
  29. 29.
    Phillips LS, Harp JB, Goldstein S, Klein J, Pao CI (1990) Regulation and action of insulin-like growth factors at the cellular level. Proc Nutr Soc 49: 451–458.Google Scholar
  30. 30.
    Harp J, Goldstein S, Sertich G, Phillips L (1989) Regulation of hepatic IGF-1 production by amino acids. Clin Res 37 (abstract).Google Scholar
  31. 31.
    Phillips LS, Goldstein S, Pao CI (1991) Nutrition and somatomedin. XXVI. Molecular regulation of IGF-I by insulin in cultured rat hepatocytes. Diabetes 40: 1525–1530.Google Scholar
  32. 32.
    Conover CA, Butler PC, Wang M, Rizza RA, Lee PD (1990) Lack of growth hormone effect on insulin-associated suppression of insulin-like growth factor binding protein 1 in humans. Diabetes 39: 1251–1256.Google Scholar
  33. 33.
    Suikkari AM, Koivisto VA, Rutanen EM, Yki-Jarvinen H, Karonen SL, Seppala M (1988) Insulin regulates the serum levels of low molecular weight insulin-like growth factor-binding protein. J Clin Endocrinol Metab 66: 266–272.Google Scholar
  34. 34.
    Rosen CJ (2000) Growth hormone and aging. Endocrine 12: 197–201.Google Scholar
  35. 35.
    Singh MA, Ding W, Manfredi TJ, et al. (1999) Insulin-like growth factor I in skeletal muscle after weight-lifting exercise in frail elders. Am J Physiol 277: E135–E143.Google Scholar
  36. 36.
    Signorello LB, Brismar K, Bergstrom R, et al. (1999) Insulin-like growth factor-binding protein-1 and prostate cancer. J Natl Cancer Inst 91: 1965–1967.Google Scholar
  37. 37.
    Cohen P, Clemmons DR, Rosenfeld RG (2000) Does the GH-IGF axis play a role in cancer pathogenesis? Growth Horm IGF Res 10: 297–305.Google Scholar
  38. 38.
    Kaplan PJ, Mohan S, Cohen P, Foster BA, Greenberg NM (1999) The insulin-like growth factor axis and prostate cancer: lessons from the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Cancer Res 59: 2203–2209.Google Scholar
  39. 39.
    Cohen P (1998) Serum insulin-like growth factor-I levels and prostate cancer risk-interpreting the evidence. J Natl Cancer Inst 90: 876–879.Google Scholar
  40. 40.
    Ornish DM, Lee KL, Fair WR, Pettengill EB, Carroll PR (2001) Dietary trial in prostate cancer: early experience and implications for clinical trial design. Urology 57: 200–201.Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Tung H. Ngo
    • 1
  • R. James Barnard
    • 1
    • 2
    • 3
  • Christopher N. Tymchuk
    • 1
  • Pinchas Cohen
    • 4
  • William J. Aronson
    • 5
  1. 1.Departments of Physiological ScienceUniversity of CaliforniaLos AngelesUSA
  2. 2.Department of Physiological ScienceUniversity of CaliforniaLos Angeles
  3. 3.Los AngelesUSA
  4. 4.PediatricsUniversity of CaliforniaLos AngelesUSA
  5. 5.UrologyUniversity of CaliforniaLos AngelesUSA

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