Summary
The effect of estramustine (EM), estradiol-17β (E2) or 5α-dihydrotestosterone (DHT) on the growth of two human prostatic carcinoma cell lines, LNCaP and LNCaP-r was investigated. The hormone resistant subline LNCaP-r was derived in our laboratory, from the hormone sensitive LNCaP cell line. E2, 10-8 or 10-5 M inhibited the growth of the LNCaP cells, but did not affect the LNCaP-r. DHT, 10-8 M, had a stabilizing effect at the stationary phase on the growth of the LNCaP cells whereas at higher concentrations, 10-5 M, the growth rate was decreased. The LNCaP-r cell line was previously reported to be unaffected by DHT. EM inhibited the growth of both cell lines but LNCaP was more sensitive than LNCaP-r. E2 and DHT modulated the effect of EM. When treated with 10-7 M EM, addition of E2 or DHT (10-7–10-5 M) further inhibited the growth. When EM was used at a higher concentration (10-5 M), the enhanced effect of growth inhibition by hormone addition was lost. Based on these results it is suggested that the presence of endogenous hormones, or estrogens released from EM on hydrolysis, may play a contributory role in the cytotoxicity of estramustine.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Murphy GP (1980) In: Models for prostate cancer, Liss, New York
Horoszewicz JS, Leong SS, Chu TM, Wajsman ZL, Friedman M, Papsidero L, Kim U, Chai LS, Kakati S, Arya SK, Sandberg AA (1980) The LNCaP cell line — a new model for studies on human prostatic carcinoma. In: Murphy GP (ed) Models for prostate cancer. Liss, New York, pp 115–132
Horoszewicz JS, Leong SS, Kawinski E, Karr JP, Rosenthal H, Chu TM, Mirand EA, Murphy GP (1983) LNCaP model of human prostatic carcinoma. Cancer Res 43:1809–1818
Hasenson M, Hartley-Asp B, Kihlfors C, Lundin A, Gustafsson J-Å, Pousette Å (1985) Effect of hormones on growth and ATP content of a human prostatic carcinoma cell line, LNCaP-r. Prostate 7:183–194
Garewal HS, Ahmann FR, Woo L (1984) ATP levels provide a useful assay for the quantitation of growth and drug effects in malignant cells. Clin Res 32:415A
Garewal HS, Ahmann FR, Celniker A (1985) The ATP assay: Anticancer drug effects on malignant cell growth. Proc Am Ass Cancer Res 26:1317A
Garewal HS, Ahmann FR, Schifman RB, Celniker A (1986) ATP assay: Ability to distinguish cytostatic from cytocidal anticancer drug effects. J Natl Cancer Inst 77:1039–1045
Kangas L, Grönroos M, Nieminen AL (1984) Bioluminescence of cellular ATP: a new method for evaluating cytotoxic agents in vitro. Med Biol 62:338–343
Lundin A, Hasenson M, Persson J, Pousette Å (1986) Estimation of biomass in growing cell lines by ATP assay. In: Colowick SP, Kaplan NO (eds) Methods in enzymology, vol 133. Part B: Bioluminescence and chemiluminescence. Academic Press, Orlando, pp 27–42
Jönsson G, Högberg B, Nilsson T (1977) Treatment of advanced prostatic carcinoma with estramustine phosphate. Scand Urol Nephrol 11:231–238
Jönsson G, Högberg B (1971) Treatment of advanced prostatic carcinoma with Estracyt. Scand J Urol Nephrol 5:103–107
Forsgren B, Björk P, Carlström K, Gustafsson J-Å, Pousette Å, Högberg B (1979) Purification and distribution of a major protein in rat prostate that binds estramustine, a nitrogen mustard derivative of estradiol-17β. Proc Nat Acad Sci USA 76:3149–3153
Forsgren B, Gustafsson J-Å, Pousette Å, Högberg B (1979) Binding characteristics of a major protein in rat ventral prostate cytosol that interacts with estramustine, a nitrogen mustard derivative of estradiol-17ß. Cancer Res 39:5155–5164
Pousette Å, Björk P, Carlström K, Forsgren B, Gustafsson J-Å, Högberg B (1980) On the presence of “prostatic secretion protein” in different species. Acta Chem Scand [B] 34:155–156
Björk P, Forsgren B, Gustafsson J-Å, Pousette Å, Högberg B (1982) Partial characterization and quantitation of a human prostatic estramustine binding protein. Cancer Res 42:1935–1942
Appelgren L-E, Forsgren B, Gustafsson J-Å, Pousette Å, Högberg B (1978) Autoradiographic studies of 3H-estramustine in the rat ventral prostate. Acta Pharamcol Toxicol 43:368–374
Högberg B, Björk P, Carlström K, Forsgren B, Gustafsson J-Å, Hökfelt T, Pousette Å (1979) The interaction of steroidal alkylating agents with binding component in the soluble fraction of the prostate. In: Murphy GP, Sandberg AA (eds) Prostate cancer and hormone receptors. Liss, New York, pp 181–199
Hartley-Asp B (1984) Estramustine induced mitotic arrest in two human prostatic carcinoma cell lines, DU 145 and PC-3. Prostate 5:93–100
Wallin M, Deinum J, Fridén B (1985) Interaction of estramustine phosphate with microtubule associated proteins. FEBS Lett 179:289–293
Kanje M, Deinum J, Wallin M, Ekström P, Edström A, Hartley-Asp B (1985) Effect of estramustine phosphate on the assembly of isolated bovine brain microtubules and fast axonal transport in the frog sciatic nerve. Cancer Res 45:2234–2239
Stearns ME, Tew KD (1985) Antimicrotuble effects of estramustine, an antiprostatic tumor drug. Cancer Res 45:3891–3897
Fritjofsson Å, Björk P, Gunnarsson PO, Norlén BS (1983) Binding and accumulation of active metabolites in tumours from prostatic cancer patients treated with Estracyt. Preliminary report. 13th International Congress of Chemotherapy, Vienna
Kruse E, Johanson SA, Hartley-Asp B, Gunnarsson PO (1988) Distribution and metabolism of estramustine in Heta cells and the human prostatic tumour cell line 1013L. Biochem Pharmacol 37:3161–3167
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hansenson, M., Lundh, B., Hartley-Asp, B. et al. Growth inhibiting effect of estramustine on two prostatic carcinoma cell lines, LNCaP and LNCaP-r. Urol. Res. 16, 357–361 (1988). https://doi.org/10.1007/BF00256042
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00256042