Abstract
Responses to coumarin have been reported for patients suffering from malignant melanoma, metastatic renal carcinoma and, recently, advanced prostate cancer. These data together with some experimental evidence for antiprostatic effect prompted us to study the activity of coumarin in various prostate tumour models and evaluate the endocrine properties of this drug. In rats no antiandrogenic activity was found. The growth of Noble Nb-R prostate tumours of the rat was strongly inhibited by coumarin (40 mg/kg; administered three times per week), whereas the hormonally more sensitive Dunning R3327-G rat prostate carcinoma did not respond to coumarin (40 mg) even when the drug was administered daily. Coumarin was also shown to posses antimetastatic activity in a Dunning R3327-MatLu tumour model. In this model small pieces of the hormone-independent tumour were implanted into the ear of the animal and later resected to mimic the clinical situation where primary tumours have been removed. The number of lung metastases was reduced significantly by 40%–50% following the administration of coumarin (40 mg daily).
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Angerer E von, Birnböck H, Kager M, Maucher A (1992) The effect of a combination of zindoxifene and cisplatins on Dunning R3327-G prostatic carcinomas of the rat. J Cancer Res Clin Oncol 118:339–343
Angerer E von, Prekajac J, Berger MR (1985) The inhibitory effect of 5-acetoxy-2-(4-acetoxyphenyl)-1-ethyl-3-methylindole (D 16726) on estrogen-dependent mammary tumors. Eur J Cancer Clin Oncol 21:531–537
Berkarda B, Bouffard-Eyuboglu H, Derman U (1983) The effect of coumarin-derivatives on the immunological system of man. Agents Actions 13:50–52
Cohen AJ (1979) Critical review of the toxicology of coumarin with special reference to interspecies differeces in metabolism and hepatotoxic response and their significance to man. Food Cosmet Toxicol 17:277–289
Kadmon D, Heston WDW, Fair WR (1982) Treatment of a metastatic prostate derived tumor with surgery and chemotherapy. J Urol 127:1238–1242
Kager M, Spruß T, Schneider MR, Angerer E von (1991) Dunning R3327-G prostate carcinoma of the rat: an appropriate model for drug evaluation. J Cancer Res Clin Oncol 118:334–338
Knebel NG, Angerer E von (1991) 2-Phenylindole linked (2-aminoalkylpyridine)dichloroplatinum(II): complexes with a selective action on estrogen receptor positive mammary tumors. J Med Chem 34:2145–2152
Lazan DW, Heston WDW, Kadmon D, Fair WR (1982) Inhibition of the R3327MAT-Lu prostatic tumor by diethylstilbestrol and 1,2-bis (3,5-dioxopiperazin-1-yl)propane. Cancer Res 42:1390–1394
Marshall EM, Mendelsohn L, Butler K, Riley L, Cantrell J, Wiseman C, Taylor R, MacDonald SS (1987) Treatment of metastatic renal cell carcinoma with coumarin (1,2-benzopyrone) and cimetidine: a pilot study. Clin Oncol 5:862–866
Marshall ME, Conley D, Hollingworth P, Brown S, Thompson JS (1989a) Effects of coumarin (1,2-benzopyrone) on lymphocyte, natural killer cell and monocyte functions in vitro. J Biol Response Mod 8:70–85
Marshall ME, Riley LK, Rhoades J, Eichhorn T, Jennings CD, Cibull M, Thompson J (1989b) Effects of coumarin (1,2-benzopyrone) and cimetidine on peripheral blood lymphocytes, natural killer cells, and monocytes in patients with advanced malignancies. J Biol Response Mod 8:62–69
Marshall ME, Butler K, Hermansen D (1990) Treatment of hormone-refractory stage D carcinoma of prostate with coumarin (1,2-benzopyrone) and cimetidine: a pilot study. Prostate 17:95–99
Mohler JL, Gomella LG, Crawford ED, Glode LM, Zippe CD, Fair WR, Marshall ME (1992) Phase II evaluation of coumarin (1,2-benzopyrone) in metastatic prostatic carcinoma. Prostate 20:123–131
Omarbasha B, Heston WDW, Huryk R, Fair WR (1988) Treatment of metastatic prostate derived tumor with cimetidine and coumarin (abstract). J Urol 134:176
Omarbasha B, Fair WR, Heston WDW (1989) Effect of coumarin on the normal rat prostate and on the R-3327H prostatic adenocarcinoma. Cancer Res 49:3045–3049
Rosskopf F, Kraus J, Franz G (1992) Immunological and antitumor effects of coumarin and some derivatives Pharmazie 47:139–142
Schneider MR, Angerer E von, Höhn W, Sinowatz F (1987) Antitumor activity of antiestrogenic phenylindoles on experimental prostate tumors. Eur J Cancer Clin Oncol 23:1005–1015
Schneider MR, Humm A, Graf AH (1990) The tumor-inhibiting effect of diethylstilbestrol and its diphosphonate on the Nb-H and Nb-R prostatic carcinomas of the rat. J Cancer Res Clin Oncol 116:159–167
Schneider MR, Schiller CD, Humm A, Angerer E von (1991) Effect of zindoxifene on experimental prostatic tumours of the rat. J Cancer Res Clin Oncol 117:33–36
Stuhlmeier K, Theyer G, Baumgartner G, Zlabinger GJ (1991) Synergistic effect of coumarin (1,2-benzopyrone) and endotoxin in the induction of human interleukin-1. Clin Exp Immunol 84:317–323
Thornes RD, Lynch G, Sheehan MV (1982) Cimetidine and coumarin therapy of melanoma. Lancet ii:328
Tseng A (1990) Effects of coumarin (1,2-benzopyrone) on ras-ancogene containing cell lines. J Cancer Res Clin Oncol 116:970
Zanker KS, Blumei G, Lange J (1984) Coumarin in melanoma patients: an experimental and clinical study. Drug Exp Clin Res 20:767–774
Author information
Authors and Affiliations
Additional information
Dedicated to Professor N. Brock on the occasion of his 80th birthday
Rights and permissions
About this article
Cite this article
Maucher, A., Kager, M. & von Angerer, E. Evaluation of the antitumour activity of coumarin in prostate cancer models. J Cancer Res Clin Oncol 119, 150–154 (1993). https://doi.org/10.1007/BF01229529
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01229529