Comment in:
Inhibition of breast cancer growth by suramin.
Vignon F, Prebois C, Rochefort H.
Institut National de la Santé et de la Recherche Médicale, Unit 148 on Hormones and Cancer, Montpellier, France.
In this study, the polyanionic compound suramin was shown to be a potent in vitro growth inhibitor of both hormone-insensitive, estrogen receptor-negative human breast cancer cells (MDA MB231 and SK-BR-3) and hormone-responsive, estrogen receptor-positive human breast cancer cells (ZR 75-1, T47D, and MCF7). The inhibitory effect of suramin was dose dependent, with a median effective dose varying from 7 microM for MDA MB231 cells to 50 microM for MCF7 cells. This result indicated that estrogen receptor-negative cells were more sensitive to the drug. In MCF7 cells, not only did suramin block the mitogenic action of growth factors such as epidermal growth factor (EGF) and insulin-like growth factors I and II (IGF-I and IGF-II, respectively), but it also totally abolished the increase in cell proliferation induced by the steroid hormone 17 beta-estradiol (E2). Maximal inhibition was obtained after 5 days of suramin treatment, and inhibition either was partially reversed by E2, IGF-I, and IGF-II or was not reversible by EGF following removal of drug. In addition, suramin significantly decreased synthesis and secretion of the lysosomal enzyme cathepsin D, which was shown to be associated with a high risk of breast tumor metastasis. These results therefore suggest that, because of its effects on growth and cathepsin D secretion, suramin might be a helpful additional therapeutic tool for breast cancer patients, especially for patients with estrogen receptor-negative tumors which are insensitive to antihormonal strategies.
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PMID: 1738172 [PubMed - indexed for MEDLINE]