Inhibition of breast cancer growth by suramin.
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.
Vignon
F
F
Institut National de la Santé et de la Recherche Médicale, Unit 148 on Hormones and Cancer, Montpellier, France.
Prebois
C
C
Rochefort
H
H
D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D002402:Cathepsin D / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors; D004965:Estrogen Antagonists / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors; D007335:Insulin-Like Growth Factor II / Q000037:antagonists & inhibitors; D013498:Suramin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004965:Estrogen Antagonists; D006131:Growth Inhibitors; D013498:Suramin; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D002402:Cathepsin D