Cancer and Metastasis Reviews

, Volume 23, Issue 3–4, pp 351–366 | Cite as

Opioid peptides in cancer

  • Jakub Fichna
  • Anna Janecka


Opioid and somatostatin systems are two main inhibitory systems in mammals implicated in a variety of processes from hormone secretion to the modulation of cell proliferation. Opioids and opioid receptors were found in a great diversity of primary human tumors and in various cancer cell lines. A new area of interest that has developed since the early 1980s has been concerned with the role of endogenous opioid systems in the growth of normal and abnormal tissues and cells.

This review presents recent developments on the identification of opioid ligands and receptors in different types of human neoplasia. It also deals with the mechanisms of opioid peptide action in carcinoma and the involvement of opioids in the regulation of tumor growth.

opioid peptides opioid peptide analogs opioid receptors carcinogenesis carcinoma 


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  1. 1.
    Hollt V: Opioid peptide processing and receptor selectivity. Annu Rev Pharmacol Toxicol 26: 59–77, 1986PubMedGoogle Scholar
  2. 2.
    Margioris AN, Liotta AS, Vaudry H, Bardin CW, Krieger DT: Characterization of immunoreactive proopiomelanocortin-related peptides in rat testes. Endocrinology 113: 663–671, 1983PubMedGoogle Scholar
  3. 3.
    Douglass J, Cox B, Quinn B, Civelli O, Herbert E: Expression of the prodynorphin gene in male and female mammalian reproductive tissues. Endocrinology 120: 707–713, 1987PubMedGoogle Scholar
  4. 4.
    Castanas E, Giraud P, Audigier Y, Drissi R, Boudouresque F, Conte-Devolx B, Oliver C: Opiate binding sites spectrum on bovine adrenal medullas and six human pheochromocytomas. Life Sci 33(Suppl 1): 295–298, 1983PubMedGoogle Scholar
  5. 5.
    Giraud P, Castanas E, Oliver C, Conte-Devolx B, Boudouresque F, Taquet H, Orlando M, Jaquet P, Eiden L, Cesselin F, Gunz G, Trigano M: Enkephalins in human pheochromocytoma biosynthesis and secretion. Eur Heart J 3(Suppl C): 19–22, 1982Google Scholar
  6. 6.
    Roy S, Loh HH: Effects of opioids on the immune system. Neurochem Res 21: 1375–1386, 1996PubMedGoogle Scholar
  7. 7.
    Scharrer B, Stefano GB: Neuropeptides and immunoregulation. In Neuropeptides and Immunoregulation. Springer Verlag, Berlin, 1994Google Scholar
  8. 8.
    Stefano GB, Scharrer B, Smith EM, Hughes TK Jr., Magazine HI, Bilfinger TV, Hartman AR, Fricchione GL, Liu Y, Makman MH: Opioid and opiate immunoregulatory processes. Crit Rev Immunol 16: 109–144, 1996PubMedGoogle Scholar
  9. 9.
    McLaughlin PJ: Opioid antagonist modulation of rat heart development. Life Sci 54: 1423–1431, 1994PubMedGoogle Scholar
  10. 10.
    Zagon IS, McLaughlin PJ: The role of endogenous opioids and opioid receptors in human and animal cancers. In Stress and Immunity. Plotnikoff NP, Murgo AJ, Faith RE, Wybran J, eds. CRC, Caldwell NJ, 343–356, 1991Google Scholar
  11. 11.
    Zagon IS, McLaughlin PJ: Identification of opioid peptides regulating proliferation of neurons and glia in the developing nervous system. Brain Res 542: 318–323, 1991PubMedGoogle Scholar
  12. 12.
    Zagon IS, McLaughlin PJ: Receptors in the developing nervous system, Volume 1. Growth factors and hormones. Chapman and Hall, London, 39–62, 1993Google Scholar
  13. 13.
    Zagon IS, Wu Y, McLaughlin PJ: Opioid growth factor inhibits DNA synthesis in mouse tongue epithelium in a circadian rhythm-dependent manner. Am J Physiol 267(3 Pt 2): R645–R652, 1994PubMedGoogle Scholar
  14. 14.
    Nyberg F, Sanderson K, Glamsta EL: The hemorphins: A new class of opioid peptides derived from the blood protein hemoglobin. Biopolymers 43: 147–156, 1997PubMedGoogle Scholar
  15. 15.
    Zhao Q, Garreau I, Sannier F, Piot JM: Opioid peptides derived from hemoglobin: Hemorphins. Biopolymers 43: 75–98, 1997PubMedGoogle Scholar
  16. 16.
    Zioudrou C, Streaty RA, Klee WA: Opioid peptides derived from food proteins. The exorphins. J Biol Chem 254: 2446–2449, 1979PubMedGoogle Scholar
  17. 17.
    Brantl V, Teschemacher H, Henschen A, Lottspeich F: Novel opioid peptides derived from casein (beta-casomorphins). I. Isolation from bovine casein peptone. Hoppe Seylers Z Physiol Chem 360: 1211–1216, 1979PubMedGoogle Scholar
  18. 18.
    Meisel H: Biochemical properties of regulatory peptides derived from milk proteins. Biopolymers 43: 119–128, 1997PubMedGoogle Scholar
  19. 19.
    Kampa M, Loukas S, Hatzoglou A, Martin P, Martin PM, Castanas E: Identification of a novel opioid peptide (Tyr-Val-Pro-Phe-Pro) derived from human alpha S1 casein (alpha S1-casomorphin and alpha S1-casomorphin amide). Biochem J 319(Pt 3): 903–908, 1996PubMedGoogle Scholar
  20. 20.
    Kampa M, Bakogeorgou E, Hatzoglou A, Damianaki A, Martin PM, Castanas E: Opioid alkaloids and casomorphin peptides decrease the proliferation of prostatic cancer cell lines (LNCaP, PC3 and DU145) through a partial interaction with opioid receptors. Eur J Pharmacol 335: 255–265, 1997PubMedGoogle Scholar
  21. 21.
    Raynor K, Kong H, Law S, Heerding J, Tallent M, Livingston F, Hines J, Reisine T: Molecular biology of opioid receptors. NIDA Res Monogr 161: 83–103, 1996PubMedGoogle Scholar
  22. 22.
    Reisine T, Bell GI: Molecular biology of opioid receptors. Trends Neurosci 16: 506–510, 1993PubMedGoogle Scholar
  23. 23.
    Castanas E, Bourhim N, Giraud P, Boudouresque F, Cantau P, Oliver C: Interaction of opiates with opioid binding sites in the bovine adrenal medulla: I. Interaction with delta and mu sites. J Neurochem 45: 677–687, 1985PubMedGoogle Scholar
  24. 24.
    Castanas E, Bourhim N, Giraud P, Boudouresque F, Cantau P, Oliver C: Interaction of opiates with opioid binding sites in the bovine adrenal medulla: II. Interaction with kappa sites. J Neurochem 45: 688–699, 1985PubMedGoogle Scholar
  25. 25.
    Reisine T, Law SF, Blake A, Tallent M: Molecular mechanisms of opiate receptor coupling to G proteins and effector systems. Ann NY Acad Sci 780: 168–175, 1996PubMedGoogle Scholar
  26. 26.
    Lundberg JM, Hamberger B, Schultzberg M, Hokfelt T, Granberg PO, Efendic S, Terenius L, Goldstein M, Luft R: Enkephalin-and somatostatin-like immunoreactivities in human adrenal medulla and pheochromocytoma. Proc Natl Acad Sci USA 76: 4079–4083, 1979PubMedGoogle Scholar
  27. 27.
    Zagon IS, McLaughlin PJ, Goodman SR, Rhodes RE: Opioid receptors and endogenous opioids in diverse human and animal cancers. J Natl Cancer Inst 79: 1059–1065, 1987PubMedGoogle Scholar
  28. 28.
    Roth KA, Bensch KG, Hoffman AR: Characterization of opioid peptides in human thyroid medullary carcinoma. Cancer 59: 1594–1598, 1987PubMedGoogle Scholar
  29. 29.
    Bostwick DG, Null WE, Holmes D, Weber E, Barchas JD, Bensch KG: Expression of opioid peptides in tumors. N Engl J Med. 317: 1439–1143, 1987PubMedGoogle Scholar
  30. 30.
    Scholar EM, Violi L, Hexum TD: The antimetastatic activity of enkephalin-like peptides. Cancer Lett 35: 133–138, 1987PubMedGoogle Scholar
  31. 31.
    Kita T, Kikuchi Y, Oomori K, Nagata I: Effects of opioid peptides on the tumoricidal activity of spleen cells from nude mice with or without tumors. Cancer Detect Prev 16: 211–214, 1992PubMedGoogle Scholar
  32. 32.
    Scopsi L, Balslev E, Brunner N, Poulsen HS, Andersen J, Rank F, Larsson LI: Immunoreactive opioid peptides in human breast cancer. Am J Pathol 134: 473–479, 1989PubMedGoogle Scholar
  33. 33.
    Cerpa-Poljak A, Lahnstein J, Mason KE, Smythe GA, Duncan MW: Mass spectrometric identification and quantification of hemorphins extracted from human adrenal and pheochromocytoma tissue. J Neurochem 68: 1712–1719, 1997PubMedGoogle Scholar
  34. 34.
    Reubi JC: Central nervous system-mediated growth inhibition of a rat prostate carcinoma by an opioid. J Endocrinol 107: 247–250, 1985PubMedGoogle Scholar
  35. 35.
    Hatzoglou A, Bakogeorgou E, Castanas E: The antiproliferative effect of opioid receptor agonists on the T47D human breast cancer cell line, is partially mediated through opioid receptors. Eur J Pharmacol 296: 199–207, 1996PubMedGoogle Scholar
  36. 36.
    Maneckjee R, Biswas R, Vonderhaar BK: Binding of opioids to human MCF-7 breast cancer cells and their effects on growth. Cancer Res 50: 2234–2238, 1990PubMedGoogle Scholar
  37. 37.
    Hytrek SD, Smith JP, McGarrity TJ, McLaughlin PJ, Lang CM, Zagon IS: Identification and characterization of zeta-opioid receptor in human colon cancer. Am J Physiol 271(1 Pt 2): R115–R121, 1996PubMedGoogle Scholar
  38. 38.
    Hatzoglou A, Gravanis A, Margioris AN, Zoumakis E, Castanas E: Identification and characterization of opioid binding sites present in the Ishikawa human endometrial adenocarcinoma cell line. J Clin Endocrinol Metab 80: 418–423, 1995PubMedGoogle Scholar
  39. 39.
    Chatikhine VA, Chevrier A, Chauzy C, Duval C, d'Anjou J, Girard N, Delpech B: Expression of opioid peptides in cells and stroma of human breast cancer and adenofibromas. Cancer Lett 77: 51–56, 1994PubMedGoogle Scholar
  40. 40.
    Francois A, Chatikhine VA, Chevallier B, Ren GS, Berry M, Chevrier A, Delpech B: Neuroendocrine primary small cell carcinoma of the breast. Report of a case and review of the literature. Am J Clin Oncol 18: 133–138, 1995PubMedGoogle Scholar
  41. 41.
    Ferri GL, Watkinson A, Dockray GJ: Proenkephalin A-derived peptides in the human gut. Gastroenterology 95: 1011–1017, 1988PubMedGoogle Scholar
  42. 42.
    Zagon IS, Hytrek SD, McLaughlin PJ: Opioid growth factor tonically inhibits human colon cancer cell proliferation in tissue culture. Am J Physiol 271: R511–R518, 1996PubMedGoogle Scholar
  43. 43.
    Yoshimasa T, Nakao K, Ikeda Y, Sakamoto M, Suda M, Imura H: Methionine-enkephalin, leucine-enkephalin methionine-enkephalin-Arg6-Phe7 and methionine-enkephalin-Arg6-Gly7-Leu8 in human pheochromocytoma. Life Sci 33(Suppl 1): 85–88, 1983PubMedGoogle Scholar
  44. 44.
    Suda T, Tozawa F, Tachibana S, Demura H, Shizume K, Sasaki A, Mouri T, Miura Y: Multiple forms of immunoreactive dynorphin in human pituitary and pheochromocytoma. Life Sci 32: 865–870, 1983PubMedGoogle Scholar
  45. 45.
    Yoshimasa T, Nakao K, Oki S, Tanaka I, Nakai Y, Imura H: Presence of dynorphin-like immunoreactivity in pheochromocytomas. J Clin Endocrinol Metab 53: 213–214, 1981PubMedGoogle Scholar
  46. 46.
    Deftos LJ, Bone HG 3rd, Parthemore JG: Immunohistological studies of medullary thyroid carcinoma and C cell hyperplasia. J Clin Endocrinol Metab 51: 857–862, 1980PubMedGoogle Scholar
  47. 47.
    Steenbergh PH, Hoppener JWM, Zandberg J, Roos BA, Jansy HS, Lips CJM: Expression of the pro-opiomelanocrtin gene in human medullary thyroid carcinoma. J Clin Endocrinol Metab 58: 904–908, 1984PubMedGoogle Scholar
  48. 48.
    Gillies G, Ratter S, Grossman A, Gaillard R, Lowry PJ, Besser GM, Rees LH: Secretion of ACTH, LPH and beta-endophin from human pituitary tumors in vitro. Clin Endocrinol (Oxf) 13: 197–205, 1980Google Scholar
  49. 49.
    Suda T, Tozawa F, Yamaguchi H, Shibasaki T, Demura H, Shizume K: Multiple forms of immunoreactive beta-endorphin are present in an ectopic adrenocorticotropin-producing tumor but not in normal pituitary or pituitary adenomas. J Clin Endocrinol Metab 54: 167–171, 1982PubMedGoogle Scholar
  50. 50.
    Pullan PT, Clement-Jones V, Corder R, Lowry PJ, Rees GM, Rees LH, Besser GM, Macedo MM, Galvao-Teles A: Ectopic production of methionine enkephalin and beta-endorphin. Br Med J 280: 758–759, 1980PubMedGoogle Scholar
  51. 51.
    Pullman PT, Clement-Jones V, Corder R, Lowry PJ, Besser GM, Rees LH: ACTH LPH and related peptides in the ectopic ACTH syndrome. Clin Endocrinol (Oxf) 13: 437–445, 1980Google Scholar
  52. 52.
    Makrigiannakis A, Margioris A, Markogiannakis E, Stournaras C, Gravanis A: Steroid hormones regulate the release of immunoreactive beta-endorphin from the Ishikawa human endometrial cell line. J Clin Endocrinol Metab 75: 584–589, 1992PubMedGoogle Scholar
  53. 53.
    Barg J, Belcheva MM, Bem WT, Lambourne B, McLachlan JA, Tolman KC, Johnson FE, Coscia CJ: Desipramine modulation of sigma and opioid peptide receptor expression in glial cells. Peptides 12: 845–849, 1991PubMedGoogle Scholar
  54. 54.
    Barg J, Belcheva MM, Levy R, McHale RJ, McLachlan JA, Johnson FE, Coscia CJ, Vogel Z: A monoclonal anti-idiotypic antibody to opioid receptors labels desipramine-induced opioid binding sites on rat C6 glioma cells and attenuates thymidine incorporation into DNA. Glia 10: 10–15, 1994PubMedGoogle Scholar
  55. 55.
    Reggiani A, Carenzi A, Della Bella D: Influence of opioids on beta-receptor down-regulation: Studies in cultured C6 glioma cells. Brain Res 423: 254–260, 1987PubMedGoogle Scholar
  56. 56.
    Bohn LM, Belcheva MM, Coscia CJ: Evidence for kappa and mu-opioid receptor expression in C6 glioma cells. J Neurochem 70: 1819–1825, 1998Google Scholar
  57. 57.
    Roth KA, Barchas JD: Small cell carcinoma cell lines contain opioid peptides and receptors. Cancer 57: 769–773, 1986PubMedGoogle Scholar
  58. 58.
    Maneckjee R, Minna JD: Opioid and nicotine receptors affect growth regulation of human lung cancer cell lines. Proc Natl Acad Sci USA 87: 3294–3298, 1990PubMedGoogle Scholar
  59. 59.
    Campa MJ, Schreiber G, Bepler G, Bishop MJ, McNutt RW, Chang KJ, Patz EF Jr.: Characterization of delta opioid receptors in lung cancer using a novel nonpeptidic ligand. Cancer Res 56: 1695–1701, 1996PubMedGoogle Scholar
  60. 60.
    Slominski A, Paus R, Wortsman J: On the potential role of proopiomelanocortin in skin physiology and pathology. Mol Cell Endocrinol 93: C1–6, 1993PubMedGoogle Scholar
  61. 61.
    Nagahama M, Funasaka Y, Fernandez-Frez ML, Ohashi A, Chakraborty AK, Ueda M, Ichihashi M: Immunoreactivity of alfa-melanocyte-stimulating hormone, adrenocorticotrophic hormone and beta-endorphin in cutaneous malignantg melanoma and benign melanocytic naevi. Br J Dermatol 138: 981–985, 1998PubMedGoogle Scholar
  62. 62.
    Krieger DT, Margioris AN, Liotta AS: Pro-opiomelanocortin-derived peptides in the rodent male reproductive tract. In Delitala G, Motta M, Serio M (eds) Opioid Modulation of Endocrine Function. Raven Press, New York NY, 1984, pp. 223–235Google Scholar
  63. 63.
    Tainio H: Peptidergic innervation of the human prostate, seminal vesicle and vas deferens. Acta Histochem 97: 113–119, 1995PubMedGoogle Scholar
  64. 64.
    Bartolome JV, Bartolome MB, Lorber BA, Dileo SJ, Schanberg SM: Effects of central administration of beta-endorphin on brain and liver DNA synthesis in preweanling rats. Neuroscience 40: 289–294, 1991PubMedGoogle Scholar
  65. 65.
    McLaughlin PJ: Regulation of DNA synthesis of myocardial and epicardial cells in developing rat heart by [Met5]enkephalin. Am J Physiol 271(1 Pt 2): R122–R129, 1996PubMedGoogle Scholar
  66. 66.
    Murgo AJ: Inhibition of B16-BL6 melanoma growth in mice by methionine-enkephalin. J Natl Cancer Inst 75: 341–344, 1985PubMedGoogle Scholar
  67. 67.
    Shahabi NA, Sharp BM: Antiproliferative effects of delta opioids on highly purified CD4+ and CD8+ murine T cells. J Pharmacol Exp Ther 273: 1105–1113, 1995PubMedGoogle Scholar
  68. 68.
    Hatzoglou A, Bakogeorgou E, Papakonstanti E, Stournaras C, Emmanouel DS, Castanas E: Identification and characterization of opioid and somatostatin binding sites in the opossum kidney (OK) cell line and their effect on growth. J Cell Biochem 63: 410–421, 1996PubMedGoogle Scholar
  69. 69.
    Panagiotou S, Hatzoglou A, Calvo F, Martin PM, Castanas E: Modulation of the estrogen-regulated proteins cathepsin D and pS2 by opioid agonists in hormone-sensitive breast cancer cell lines (MCF7 and T47D): Evidence for an interaction between the two systems. J Cell Biochem 71: 416–428, 1998PubMedGoogle Scholar
  70. 70.
    Panagiotou S, Bakogeorgou E, Papakonstanti E, Hatzoglou A, Wallet F, Dussert C, Stournaras C, Martin PM, Castanas E: Opioid agonists modify breast cancer cell proliferation by blocking cells to the G2/M phase of the cycle: Involvement of cytoskeletal elements. J Cell Biochem 73: 204–211, 1999PubMedGoogle Scholar
  71. 71.
    Rivier C, Vale W, Ling N, Brown M, Guillemin R: Stimulation in vivo of the secretion of prolactin and growth hormone by beta-endorphin. Endocrinology 100: 238–241, 1977PubMedGoogle Scholar
  72. 72.
    Johnson HM, Smith EM, Torres BA, Blalock JE: Regulation of the in vitro antibody response by neuroendocrine hormones. Proc Natl Acad Sci USA 79: 4171–4174, 1982PubMedGoogle Scholar
  73. 73.
    Blalock JE: Proopiomelanocortin-derived peptides in the immune system. Clin Endocrinol (Oxf) 22: 823–827, 1985Google Scholar
  74. 74.
    Moon TD: The effect of opiates upon prostatic carcinoma cell growth. Biochem Biophys Res Commun 153: 722–727, 1988PubMedGoogle Scholar
  75. 75.
    Lee YS, Wurster RD: Differential effects of methionine enkephalin on the growth of brain tumor cells. J Neurooncol 19: 11–15, 1994PubMedGoogle Scholar
  76. 76.
    Woll PJ: Neuropeptide growth factors and cancer. Br J Cancer 63: 469–475, 1991PubMedGoogle Scholar
  77. 77.
    Iishi H, Tatsuta M, Baba M, Okuda S, Taniguchi H: Enhancement by methionine enkephalin of colon carcinogenesis induced by azoxymethane. Cancer Res 51: 785–788, 1991PubMedGoogle Scholar
  78. 78.
    Lantz I, Glamsta EL, Talback L, Nyberg F: Hemorphins derived from hemoglobin have an inhibitory action on angiotensin converting enzyme activity. FEBS Lett 287: 39–41, 1991PubMedGoogle Scholar
  79. 79.
    Zhao Q, Sannier F, Garreau I, Guillochon D, Piot JM: Inhibition and inhibition kinetics of angiotensin converting enzyme activity by hemorphins, isolated from a peptic bovine hemoglobin hydrolysate. Biochem Biophys Res Commun 204: 216–223, 1994PubMedGoogle Scholar
  80. 80.
    Bunn PA Jr., Chan D, Dienhart DG, Tolley R, Tagawa M, Jewett PB: Neuropeptide signal transduction in lung cancer: Clinical implications of bradykinin sensitivity and overall heterogeneity. Cancer Res 52: 24–31, 1992PubMedGoogle Scholar
  81. 81.
    Leslie FM: Methods used for the study of opioid receptors. Pharmacol Rev 39: 197–249, 1987PubMedGoogle Scholar
  82. 82.
    Zagon IS, Sassani JW, Allison G, McLaughlin PJ: Conserved expression of the opioid growth factor, [Met5]enkephalin, and the zeta (zeta) opioid receptor in vertebrate cornea. Brain Res 671: 105–111, 1995PubMedGoogle Scholar
  83. 83.
    Zagon IS, Isayama T, McLaughlin PJ: Preproenkephalin mRNA expression in the developing and adult rat brain. Brain Res Mol Brain Res 21: 85–98, 1994PubMedGoogle Scholar
  84. 84.
    Isayama T, McLaughlin PJ, Zagon IS: Endogenous opioids regulate cell proliferation in the retina of developing rat. Brain Res 544: 79–85, 1991PubMedGoogle Scholar
  85. 85.
    Zagon IS, McLaughlin P: Endogenous opioids and the growth regulation of a neural tumor. Life Sci 43: 1313–1318, 1988PubMedGoogle Scholar
  86. 86.
    Zagon IS, McLaughlin PJ: Endogenous opioid systems regulate growth of neural tumor cells in culture. Brain Res 490: 14–25, 1989PubMedGoogle Scholar
  87. 87.
    Plotnikoff NP, Miller GC: Enkephalins as immunomodulators. Int J Immunopharmacol 5: 437–441, 1983PubMedGoogle Scholar
  88. 88.
    Jankovic BD, Maric D: Enkephalins and immunity. I: In vivo suppression and potentiation of humoral immune response. Ann N Y Acad Sci 496: 115–125, 1987PubMedGoogle Scholar
  89. 89.
    Maric D, Jankovic BD: Enkephalins and immunity. II: In vivo modulation of cell-mediated immunity. Ann N Y Acad Sci 496: 126–136, 1987PubMedGoogle Scholar
  90. 90.
    Zagon IS, Roesener CD, Verderame MF, Ohlsson-Wilhelm BM, Levin RJ, McLaughlin PJ: Opioid growth factor regulates the cell cycle of human neoplasias. Int J Oncol 17: 1053–1061, 2000PubMedGoogle Scholar
  91. 91.
    Sherr CJ: Cancer cell cycles. Science 274: 1672–1677, 1996PubMedGoogle Scholar
  92. 92.
    Hartwell LH, Kastan MB: Cell cycle control and cancer. Science 266: 1821–1828, 1994PubMedGoogle Scholar
  93. 93.
    Shackney SE, Shackney TV: Cell cycle models for molecular biology and molecular oncology: Exploring new dimensions. Cytometry 35: 97–116, 1999PubMedGoogle Scholar
  94. 94.
    Pardee AB: G1 events and regulation of cell proliferation. Science 246: 603–608, 1989PubMedGoogle Scholar
  95. 95.
    Zagon IS, Verderame MF, Allen SS, McLaughlin PJ: Cloning, sequencing, chromosomal location, and function of cDNAs encoding an opioid growth factor receptor (OGFr) in humans. Brain Res 856: 75–83, 2000PubMedGoogle Scholar
  96. 96.
    Zagon IS, Verderame MF, Zimmer WE, McLaughlin PJ: Molecular characterization and distribution of the opioid growth factor receptor (OGFr) in mouse. Brain Res Mol Brain Res 84: 106–114, 2000PubMedGoogle Scholar
  97. 97.
    Zagon IS, Hytrek SD, Lang CM, Smith JP, McGarrity TJ, Wu Y, McLaughlin PJ: Opioid growth factor ([Met5]enkephalin) prevents the incidence and retards the growth of human colon cancer. Am J Physiol 271(3 Pt 2): R780–R786, 1996PubMedGoogle Scholar
  98. 98.
    Zagon IS, Verderame MF, McLaughlin PJ: The biology of the opioid growth factor receptor (OGFr). Brain Res Brain Res Rev 38: 351–376, 2002PubMedGoogle Scholar
  99. 99.
    Yoshimasa T, Nakao K, Ohtsuki H, Li S, Imura H: Methionine-enkephalin and leucine-enkephalin in human sympathoadrenal system and pheochromocytoma. J Clin Invest 69: 643–650, 1982PubMedGoogle Scholar
  100. 100.
    Crowe R, Chapple CR, Burnstock G: The human prostate gland: A histochemical and immunohistochemical study of neuropeptides, serotonine, dopamine beta-hydroxylase and acetylcholinesterase in autonomic nerves ganglia. Br J Urol 68: 53–61, 1991PubMedGoogle Scholar
  101. 101.
    Noordzij MA, van Steenbrugge GJ, van der Kwast TH, Schroder FH: Neuroendocrine cells in the normal, hyperplastic and neoplastic prostate. Urol Res 22: 333–341, 1995PubMedGoogle Scholar
  102. 102.
    Gkonos PJ, Krongrad A, Roos BA: Neuroendocrine peptides in the prostate. Urol Res 23: 81–87, 1995PubMedGoogle Scholar
  103. 103.
    VonHoff DD, Forseth B: Modulation of growth of human and murine humors by human beta-endorphin (beta-END). Abstract 932. Proc Am Assoc Cancer Res 236, 1982Google Scholar
  104. 104.
    Kampa M, Loukas S, Tsapis A, Castanas E: Receptorphin: A conserved peptide derived from the sequence of the opioid receptor, with opioid displacement activity and potent antiproliferative actions in tumor cells. BMC Pharmacol 1: 9, 2001PubMedGoogle Scholar
  105. 105.
    Hatzoglou A, Bakogeorgou E, Hatzoglou C, Martin PM, Castanas E: Antiproliferative and receptor binding properties of alfa-and beta-casomorphins in the T47D human breast cancer cell line. Eur J Pharmacol 310: 217–223, 1996PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Jakub Fichna
    • 1
  • Anna Janecka
    • 1
  1. 1.Department of Medicinal ChemistryMedical University of Lodz, LodzLodzPoland

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