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Abstract
Melatonin (aMT) appears to be a potentially important oncostatic substance that can block the mitogenic effects of tumour-promoting hormones and growth factors such as oestradiol and epidermal growth factor, in vitro. In the present study, we examined the possibility that aMT would also inhibit the stimulatory effects of the tumour-promoter prolactin (PRL) on MCF-7 and ZR75-1 human breast cancer cell (HBC) growth under 5% charcoal-stripped fetal bovine serum culture conditions. Human PRL (10-100 ng ml-1) stimulated the rate of MCF-7 and ZR-75-1 HBC growth up to 2-fold above that of untreated controls. Melatonin, at concentrations between 10(-12) M and 10(-5)M, diminished and at physiological levels completely abolished PRL's mitogenic activity, but had no effect on growth in the absence of PRL. The mitogenic effects of human growth hormone (hGH), a PRL-related hormone, and also of several monoclonal antibodies (MAbs) against the PRL receptor (PRLR), were also abrogated by physiological concentrations of aMT. Additionally, aMT blocked the enhancement of MAb mitogenic activity induced by a second 'cross-linking' antibody (CLA). These findings indicate that aMT interrupts the PRLR-mediated growth signal in HBC and suggest that the oncostatic activity of aMT may also be linked with an antagonism of PRL's actions.
Highlights
As shown in Figure la and b, PRL, at concentrations ranging from 20 to 100 ng ml1', significantly increased the rate of MCF-7 and ZR-75-1 cell growth as compared with untreated controls when cells were grown for 3 days as monolayer cultures in medium supplemented with 5% charcoal-stripped FBS (CSS) and hormone
Under the appropriate culture conditions, MCF-7 and ZR75-1 human breast cancer cells are sensitive to a number of different mitogens including the pituitary hormone PRL (Biswas and Vonderhaar, 1987; Vonderhaar, 1989)
Corroborating the reports of Biswas and Vonderhaar (1987), we found that human GH stimulated the proliferation of MCF-7 cells, which is consistent with GH's reported competitive binding to the PRL receptor (PRLR) (Murphy et al, 1984)
Summary
Human MCF-7 breast cancer cells were obtained from Dr Steven Hill of Tulane University (New Orleans, LA, USA), and from American Type Culture Collection, Rockville, MD, USA. The ZR-75-1 breast cancer cells were purchased from the American Type Culture Collection. All cells were routinely tested for mycoplasma contamination and were determined to be mycoplasma free. Antibiotics and trypan blue were obtained from Gibco (Grand Island, NY, USA). Fetal bovine serum was obtained from Gibco and Tissue Culture Biologicals (Tulare, CA, USA). Dextran T-70 was supplied by Pharmacia (Piscataway, NJ, USA).
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