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Inhibition of breast cancer growth by suramin
F Vignon1, C Prebois, H Rochefort
1Institut National de la Santé et de la Recherche Médicale, Unit 148 on Hormones and Cancer, Montpellier, France.
Abstract:
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.
Insights
Suramin effectively inhibits human breast cancer cell growth in vitro, particularly estrogen receptor-negative types. This compound also reduces cathepsin D secretion, suggesting potential as a novel breast cancer therapy.
Area of Science:
- Oncology
- Pharmacology
Background:
- Breast cancer comprises hormone-insensitive (ER-negative) and hormone-responsive (ER-positive) subtypes.
- Estrogen receptor status significantly influences treatment strategies.
- Cathepsin D is a lysosomal enzyme linked to breast tumor metastasis risk.
Purpose of the Study:
- To evaluate suramin as a potential in vitro inhibitor of human breast cancer cell growth.
- To investigate suramin's effects on hormone-responsive and hormone-insensitive breast cancer cells.
- To assess suramin's impact on cathepsin D secretion.
Main Methods:
- In vitro cell culture of human breast cancer cell lines (MDA MB231, SK-BR-3, ZR 75-1, T47D, MCF7).
- Dose-response studies to determine median effective dose (MED).
- Treatment with suramin in combination with growth factors (EGF, IGF-I, IGF-II) and 17 beta-estradiol (E2).
- Measurement of cathepsin D synthesis and secretion.
Main Results:
- Suramin demonstrated potent dose-dependent in vitro growth inhibition across all tested breast cancer cell lines.
- Estrogen receptor-negative cells exhibited higher sensitivity to suramin compared to estrogen receptor-positive cells.
- Suramin blocked mitogenic effects of EGF, IGF-I, IGF-II, and E2, with varying reversibility.
- Suramin significantly decreased cathepsin D synthesis and secretion.
Conclusions:
- Suramin is a potent in vitro inhibitor of human breast cancer cell proliferation.
- Its efficacy against estrogen receptor-negative cells suggests a potential therapeutic role, especially for resistant tumors.
- Suramin's ability to reduce cathepsin D secretion may further enhance its therapeutic utility in breast cancer treatment.