Skip to main content
Log in

Effects of the antiestrogen toremifene on growth of the human mammary carcinoma cell line MCF-7

  • Original Papers
  • Experimental Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Summary

The effects of toremifene, a new antiestrogenic drug, were investigated in vitro on the exponentially growing human mammary carcinoma cell line MCF-7. The drug effects were monitored by serial cell counts and DNA flow cytometry. The inhibitory effect of toremifene on MCF-7 became greater as the drug concentration was increased from 1 ΜM to 10 ΜM. At 5 ΜM toremifene induced a large decrease in the relative percentages of Sand G2/M-phase cells, and an increase in the amount of cell debris, indicating increased cell death. After withdrawal of the drug the mammary cancer cells resumed logarithmic growth similar to that of control cells. The effects caused by toremifene were similar to those caused by tamoxifen both in quality and quantity.

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

Abbreviations

ER:

estrogen receptor

D5:

growth medium containing 5% fetal bovine serum depleted of steroids

TGF:

transforming growth factor

Literatur

  • Alanen K, Klemi PJ, Taimela S, Joensuu H (1988) A simple preservative for flow cytometric DNA analysis. Cytometry 10:86–89

    Google Scholar 

  • Baisch H, Göhde W, Linden WA (1975) Analysis of PCP data to determine the fraction of cells in the various phases of the cell cycle. Radiat Environ Biophys 12:31–39

    Google Scholar 

  • Ben-Baruch G, Schrieber G, Sokolovsky M (1982) Cooperativity pattern in the interaction of the antiestrogen drug clomiphene with the muscarinic receptors. Mol Pharmacol 21:287–293

    Google Scholar 

  • Berry J, Green BJ, Matheson DS (1987) Modulation of natural killer cell activity by tamoxifen in stage I post-menopausal breast cancer. Eur J Cancer Clin Oncol 23:517–520

    Google Scholar 

  • Bonne C, Raynaud J-P (1976) Assay of androgen binding sites by exchange with methyltrienolone (R 1881). Steroids 27:497–507

    Google Scholar 

  • Brandes LJ, Macdonald LM, Bogdanovic RP (1985) Evidence that the antiestrogen binding site is a histamine or histamine-like receptor. Biochem Biophys Res Commun 126:905–910

    Google Scholar 

  • Brooks SC, Locke ER, Soule HD (1973) Estrogen receptor in human cell line (MCF-7) from breast carcinoma. J Biol Chem 248:6251–6253

    Google Scholar 

  • Coezy E, Borgna J-L, Rochefort H (1982) Tamoxifen and metabolites in MCF-7 cells: correlation between binding to estrogen receptor and inhibition of cell growth. Cancer Res 42:317–323

    Google Scholar 

  • DeGregorio MW, Ford JM, Benz CC, Wiebe VJ (1989) Toremifene: pharmacological and pharmacokinetic basis of reversing multidrug resistance. J Clin Oncol 9:1359–1364

    Google Scholar 

  • Dickson RB, Lippman ME (1987) Estrogenic regulation of growth and polypeptide growth factor secretion in human breast carcinoma. Endocr Rev 8:29–43

    Google Scholar 

  • Ebbs SR, Roberts JV, Baum M (1987) Alternative mechanism of action of “anti-oestrogens” in breast cancer. Lancet 11:621

    Google Scholar 

  • Grenman R, Virolainen E, Shapira A, Carey T (1987) In vitro effects of tamoxifen on UM-SCC head and neck cancer cell lines: correlation with the estrogen and progesterone receptor content. Int J Cancer 39:77–81

    Google Scholar 

  • Gulino A, Barrera G, Vacca A, Farina A, Ferretti C, Screpanti I, Dianzani MU, Frati L (1986) Calmodulin antagonism and growth-inhibiting activity of triphenylethylene antiestrogens in MCF-7 human breast cancer cells. Cancer Res 46: 6274–6278

    Google Scholar 

  • Hiemke C, Ghraf R (1984) Interactions of nonsteroidal antiestrogens with dopamine-receptor binding. J. Steroid Biochem 21:663–667

    Google Scholar 

  • Hirsimäki P, Hirsimäki Y, Nieminen L (1988) The effects of tamoxifen citrate and toremifene citrate on the ultrastructure of rat liver. In: Proc. of the 9th European Congress on Electron Microscopy (Goodhew PJ, Dickinson HG eds), York England 4.–9. 9. 1988

  • Horwitz KB, Costlow ME, McGuire WL (1975) MCF-7: a human breast cancer cell line with estrogen, androgen, progesterone, and glucocorticoid receptors. Steroids 26:785–794

    Google Scholar 

  • Jordan VC, Fritz NF, Tormey DC (1987) Long-term adjuvant therapy with tamoxifen: effects on sex hormone binding globulin and antithrombin III. Cancer Res 47:4517–4519

    Google Scholar 

  • Kallio S, Kangas L, Blanco G, Johansson R, Karjalainen A, Perilä M, Piippo I, Sundqvist H, Södervall M, Toivola R (1986) A new triphenylethylene compound, Fc-1157a. Cancer Chemother Pharmacol 17:103–108

    Google Scholar 

  • Kangas L, Nieminen A-L, Blanco G, Grönroos M, Kallio S, Karjalainen A, Perilä M, Södervall M, Toivola R (1986) A new triphenylethylene compound, Fc-1157a. II. Antitumor effects. Cancer Chemother Pharmacol 17:109–113

    Google Scholar 

  • Knabbe C, Lippman ME, Wakefield LM, Flanders KC, Kasid A, Derynck R, Dickson RB (1987) Evidence that transforming growth factor-beta is a hormonally regulated negative growth factor in human breast cancer cells. Cell 48:417–428

    Google Scholar 

  • Koga M, Sutherland RL (1987) Epidermal growth factor partially reverses the inhibitory effects of antiestrogens on T 47D human breast cancer cell growth. Biochem Biophys Res Commun 146:739–745

    Google Scholar 

  • Lam H-YP (1984) Tamoxifen is a calmodulin antagonist in the activation of cAMP phosphodiesterase. Biochem Biophys Res Commun 118:27–32

    Google Scholar 

  • Lykkesfeldt AE, Larsen JK, Christensen IJ, Briand P (1984) Effects of the antiestrogen tamoxifen on the cell cycle kinetics of the human breast cancer cell line MCF-7. Br J Cancer 49:717–722

    Google Scholar 

  • Musgrove EA, Wakeling AE, Sutherland RL (1989) Points of action of estrogen antagonists and a calmodulin antagonist within the MCF-7 human breast cancer cell cycle. Cancer Res 49:2398–2404

    Google Scholar 

  • O'Brian CA, Liskamp RM, Solomon DH, Weinstein IB (1985) Inhibition of protein kinase C by tamoxifen. Cancer Res 45:2462–2465

    Google Scholar 

  • Osborne CK, Boldt DH, Clark GM, Trent JM (1983) Effects of tamoxifen on human breast cancer cell cycle kinetics: accumulation of cells in early G1 phase. Cancer Res 43:3583–3585

    Google Scholar 

  • Reddel RR, Murphy LC, Sutherland RL (1983) Effect of biologically active metabolites of tamoxifen on the proliferation kinetics of MCF-7 human breast cancer cells in vitro. Cancer Res 43:4619–4624

    Google Scholar 

  • Ruenitz PC, Bagley JR, Pape CW (1984) Some chemical and biochemical aspects of liver microsomal metabolism of tamoxifen. Drug Metab Dispos 12:478–483

    Google Scholar 

  • Soule HD, Vazques J, Long A, Albert S, Brennan M (1973) A human cell line from a pleural effusion derived from a breast carcinoma. J Natl Cancer Inst 51:1409–1416

    Google Scholar 

  • Sutherland RL, Murphy LC, Foo MS, Green MD, Whybourne AM, Krozowski ZS (1980) High-affinity anti-oestrogen binding site distinct from the oestrogen receptor. Nature 288:273–275

    Google Scholar 

  • Sutherland RL, Hall RE, Taylor IW (1983) Cell proliferation kinetics of MCF-7 human mammary carcinoma cells in culture and effects of tamoxifen on exponentially growing and plateauphase cells. Cancer Res 43:3998–4006

    Google Scholar 

  • Taylor JS, Blanchard B, Zava DT (1984) Estrogen receptor-mediated and cytotoxic effects of antiestrogens tamoxifen and 4-hydroxytamoxifen. Cancer Res 44:1409–1414

    Google Scholar 

  • Valavaara R, Pyrhönen S, Heikkinen M, Rissanen P, Blanco G, Thölix E, Nordman E, Taskinen P, Holsti L, Hajba A (1988) Toremifene, a new antiestrogenic compound, for treatment of advanced breast cancer. Eur J Cancer Clin Oncol 24:785–790

    Google Scholar 

  • Vindelov LL, Christensen IJ, Nissen NI (1983) A detergent trypsin method for the preparation of nuclei for flow cytometric DNA analysis. Cytometry 3:323–327

    Google Scholar 

  • Virolainen E, Carey T, Wicha M, Krause CJ (1983) Factors affecting the growth of head and neck squamous carcinoma cell lines. Head-Neck Surg 91:126–135

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

The study was supported by the Cancer Society of Finland

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grenman, R., Laine, K.M., Klemi, P.J. et al. Effects of the antiestrogen toremifene on growth of the human mammary carcinoma cell line MCF-7. J Cancer Res Clin Oncol 117, 223–226 (1991). https://doi.org/10.1007/BF01625428

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01625428

Key words

Navigation