Skip to main content
Log in

Differential effects of methionine enkephalin on the growth of brain tumor cells

  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Summary

The effect of methionine enkephalin on the growth of human brain tumor cells was investigated. The results show that this endogenous opioid has dual effects on tumor cell growth. This peptide exerted an inhibitory effect in SK-N-MC human neuroblastoma cell line; in contrast, in U-373 MG human astrocytoma cell line, the peptide showed a stimulatory effect. Treatment with naltrexone, an opioid receptor antagonist, also resulted in a similar alteration of tumor cell growth implicating that its action may be unrelated to opioid receptor blockade. These results suggest that in these tumor cell lines endogenous opioid systems may be involved in cell proliferation. Furthermore, these tumor cell lines may be useful model systems for the study of the signal transduction mechanisms of endogenous opioids.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Grossman A: Opioids and stress in man. J Endocr 119: 377–381, 1988

    Google Scholar 

  2. Pleuvry BJ: Opioid receptors and their ligands: Natural and unnatural. Br J Anaesth 66: 370–380, 1991

    Google Scholar 

  3. Fischer EG, Falke NM: β-endorphin modulates immune functions. Psychother Psychosom 42: 195–204, 1984

    Google Scholar 

  4. Plotnikoff NP, Miller GC: Enkephalins as immunomodulators. Int J Immunopharmacol 5: 437–441, 1983

    Google Scholar 

  5. Simpson RH, Arbo TE, Lundy J: β-endorphin injected into the nucleus of the raphe magnus facilitates metastatic tumor growth. Brain Res Bull 12: 487–491, 1984

    Google Scholar 

  6. Iishi H, Tasuta M, Baba M, Okuda S, Taniguchi H: Enhancement by methionine enkephalin of colon carcinogenesis induced by azoxymethane. Cancer Res 51: 785–788, 1991

    Google Scholar 

  7. 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, 1990

    Google Scholar 

  8. Srisuchart B, Fuchs BA, Sikorski EE, Munson AE, Loveless SE: Antitumor activity of enkephalin analogues in inhibiting PYB6 tumor growth in mice and immunological effects of methionine enkephalinamide. Int J Immunopharmac 11: 487–500, 1989

    Google Scholar 

  9. Fox BH: Premorbid psychological factors as related to cancer incidence. J Behav Med 1: 45–133, 1978

    Google Scholar 

  10. Slomon GF, Amkraut AA: Psychoneuroendocrinological effects on the immune response. Annu Rev Microbiol 35: 155–184, 1981

    Google Scholar 

  11. Lewis JW, Shavit Y, Terman GW, Nelson LR, Gale RP, Liebeskind JC: Apparent involvement of opioid peptides in stress-induced enhancement of tumor growth. Peptides 4: 635–638, 1983

    Google Scholar 

  12. Lewis JW, Shavit Y, Terman GW, Nelson LR, Martin FC, Gale RP, Liebeskind JC: Involvement of opioid peptides in the analgesic, immunosuppressive and tumor-enhancing effects of stress. Psychopharmac Bull 21: 479–484, 1985

    Google Scholar 

  13. Zagon IS, McLaughlin PJ: Opioid antagonist modulation of murine neuroblastoma: A profile of cell proliferation and opioid peptides and receptors. Brain Res 480: 16–28, 1989

    Google Scholar 

  14. Stiene-Martin A, Hauser KF: Opioid-dependent growth of glial cultures: Suppression of astrocyte DNA synthesis by met-enkephalin. Life Sci 46: 91–98, 1990

    Google Scholar 

  15. Zagon IS, Goodman SR, McLaughlin PJ: Demonstration and characterization of zeta, a growth-related opioid receptor, in a neuroblastoma cell line. Brain Res 511: 181–186, 1990

    Google Scholar 

  16. Childers S: Opioid receptor-coupled second messenger systems. Life Sci 48: 1991–2003, 1991

    Google Scholar 

  17. North RA, Williams JT: On the potassium conductance increased by opioids in rat locus coeruleus neurons. J Physiol 364: 265–280, 1985

    Google Scholar 

  18. Wimpey TL, Chavkin C: Opioids activate both an inward rectifier and a novel voltage-gated potassium conductance in the hippocampal formation. Neuron 6: 281–289, 1991

    Google Scholar 

  19. Gross RA, Moises HC, Uhler MD, MacDonald RL: Dynorphin A and cAMP-dependent protein kinase independently regulate neuronal calcium currents. Proc Natl Acad Sci USA 87: 7025–7029, 1990

    Google Scholar 

  20. Geck P, Bereiter-Hahn J: The role of electrolytes in early stages of cell proliferation. Cell Biol Rev 25: 85–104, 1991

    Google Scholar 

  21. DeCoursey TE, Chandy KG, Gupta S, Cahalan MD: Voltage-dependent K+ channels in human T lymphocytes: A role in mitogenesis? Nature 307: 465–468, 1984

    Google Scholar 

  22. Lee YS, Sayeed MM, Wurster RD: Inhibition of cell growth by K+ channel modulators is due to interference with agonist-induced Ca2+ release. Cell Signalling 5: 803–809, 1993

    Google Scholar 

  23. Lee YS, Sayeed MM, Wurster RD: Inhibition of human brain tumor cell growth by a receptor-operated Ca2+ channel blocker. Cancer Lett 72: 77–81, 1993

    Google Scholar 

  24. Girard A, Dubois MP, Pessac B: Mise en evidence de neuropeptides dans les lignées de cellules nerveuses et non nerveuses en culture continue. C R Acad Sc Paris 294: 1051–1055, 1982

    Google Scholar 

  25. Rost N, Chaffanet M, Nissou MF, Chauvin C, Foote AM, Laine M, Benabid AL: Expression of the preproenkephalin A gene in tumor cells and brain glioma: A northern and in situ hybridization study. Neuropeptides 13: 133–138, 1989

    Google Scholar 

  26. Zagon IS, McLaughlin PJ: Heroin prolongs survival time and retards tumor growth in mice with neuroblastoma. Brain Res Bull 7: 25–32, 1981

    Google Scholar 

  27. 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, 1990

    Google Scholar 

  28. Zagon IS, MacLaughlin PJ: Naltrexone modulates tumor response in mice with neuroblastoma. Science 221: 671–673, 1983

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, Y.S., Wurster, R.D. Differential effects of methionine enkephalin on the growth of brain tumor cells. J Neuro-Oncol 19, 11–15 (1994). https://doi.org/10.1007/BF01051044

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01051044

Key words

Navigation