Potential mechanism for the effects of dexamethasone on growth of human melanoma cells in vitro

Abdel-Moneim M. Osman, Omimah A. Nasseir, Naglaa R. Ismail

.

DOI: 10.4236/health.2010.28129                

Abstract

This study deals with the inhibitory effects of dexamethsone on the proliferation of a human melanoma cell line in vitro. A retarded cell proliferation was observed in M-5A cells with the presence of specific high affinity glucocorticoid steroid receptors. There was a correlation between the number of glucococrticoid binding sites and the reduction of cell proliferation in term of reduced plating efficiency. Arrest or accumula- tion of M-5A cells in G1 phase or both in G1 and G2 phase appeared to be involved in the growth inhibitory effect by dexamethsone. The magnitude and duration of cell cycle arrest up to 72 hours were dose dependent. There was a correlation between the duration of the disturbance of the cell cycle progression in M-5A cells after dexamethsone treatment and the inhibition of cell proliferation. Synthesis of receptor protein was not specifically stimulated or inhibited relative to the effect on cellular protein content in general. This may conclude that in the melanoma M-5A cell, death after glucocorticoid treatment is somehow related to the glucocorticoid receptor content and to the disturbance of cell cycle distribution.

Keywords

Melanoma Cells; Dexamethasone; Glucocorticoid Receptors

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Shiu, M.H., Schottenfeld, D., Maclean, B. and Fortner, J.G. (1976) Adverse effect of pregnancy on melanoma. A reappraisal. Cancer, 37(1), 181-187.
[2]	Collinson, F.J., Lam, T.K., Bruijn, W.M., De Wilt, J.H., Lamont, M., Thompson, J.K. and Kefford, R.F. (2008) Long-term survival and occasional regression of distat melanoma metastases after adrenal metastectomy. Annals Surgical Oncology, 15(6), 1741-1749.
[3]	Bregman, M.D., Peters, E., Sander, D. and Meyskens, F.L. Jr. (1983) Dexamethsone, prostaglandin A and retinoic acid modulation of murine and human melanoma cells grown in soft agar. Journal of the National Cancer Institute, 71(5), 927-932.
[4]	Ramirez, M.T, Chow, A., Hirschhorn, C.D., Terwey, T.H., Hochma, A.A., Lu, S., Miles, R.C., Sakaguchi, S., Houghton, A.N. and Van den Brink, M.R. (2006) Glucocorticopid-induced TNF receptor family related gene activation overcomes tolerance/ignorance to melanoma differentiation antigens and enhances antitumor immunity. Journal of Immunology, 176(11), 6434-6442.
[5]	Banciu, M., Metselaar, J.M., Schiffelers, R.M., Storm, G. (2008) Antitumor activity of liposomal prednisolone phosphate depends on the presence of functional tumor-associated macrophages in tumor tissue. Neoplasia, 10(2), 108-117.
[6]	Liao, S.K., Dent, P.B. and McCulloch, P.B. (1971) Characterizatiof of human malignant melanoma cell lines. I. morphology and growth characteristics in culture. Journal of the National Cancer Institute, 54(5), 1037-1044.
[7]	Rosner, B.A. and Cristofalo, V.J. (1981) Changes in specific dexamethsone binding during aging in WI-38 cells. Endocrinology, 108(5), 1965-1971.
[8]	Lowry, O.H., Rosenbrough, N.J., Farr, A.L. and Randall, R.J. (1951) Protein measurement with the folin phenol reagent. Journal of Biological Chemistry, 193(1), 265- 275
[9]	Smets, L.A., Bout, B., Brouwer, M. and Tulp, A. (1983) Cytotoxic effect of dexamethsone restricted to noncycling, early G1 phase cells of L1210 leukemia. Journal of Cellular Physiology, 116(3), 397-403.
[10]	McCarthy, W.H., Black, A.L. and Milton, G.W. (1980) Melanoma in New South Wales: An epidemiologic survey 1970-1976. Cancer, 46(2), 427-432.
[11]	Nathanson, L. (1983) Epidemiologic and etiologic considerations in malignant melanoma. In: Costanzi, J.J., Ed., Malignant Melanoma 1, Cancer Treatment and Research, 9, 1-27.
[12]	Comis, R.L. (1976) DTIC (NSC-45388) in malignant melanoma: A perspective. Cancer Treatment Reports, 60(2), 165-176.
[13]	Costanzi, J.J. (1983) The chemotherapy of malignant melanoma. In: Costanzi, J.J., Ed., Malignant melanoma 1. Cancer Treatment and Research, 9, 259-274.
[14]	Ristic-Fira, A., Vujcic, M., Krstic-Demonacos, M. and Kanazir, D. (1999) Identification and characterization of glucocorticoid receptors in B16 mouse melanoma cells. Endocrine Regulations, 33(3), 109-115.
[15]	Shipman, G.F., Bloomfield, C.D., Smith, K.A., Peterson, B.A. and Munck, A. (1981). The effect of glucocorticoid therapy on glucocorticoid receptors in leukemia and lymphoma. Blood, 58(6), 1198-1202.
[16]	Shipman, G.F., Bloomfield, C.D., Gajl-Peczalaska, K.L., Munck, A.U. and Smith, K.A. (1983) Glucocrticoid and lymphocytes.III. Effect of glucocoorticoid administration on lymphocyte glucocorticoid receptors. Blood, 61(6), 1086-1090.
[17]	Dobos, J. (2009) Endocrine factors influencing melanoma progression. Magyar Onkologia Journal, 53(1), 47-50.