Suramin inhibits cell proliferation in ovarian and cervical cancer by downregulating heparanase expression.

BACKGROUND: Aberrant expression of heparanase (Hpa) is associated with apoor prognosis in ovarian and cervical cancer patients. Inhibitors of Hpa can prevent the growth and metastasis of malignant tumor cells, and suramin may be such a compound that has strong anti-proliferative effects on several kinds of cancer cells. We have therefore tested whether the growth inhibiting effect of suramin on ovarian and cervical cancer cells is due to downregulation of Hpa expression. RESULTS: Suramin at 300-600 μg/ml significantly inhibited HO-8910 PM and HeLa cell growth at 24 h, in both a time-dependent and dose-dependent manner, with an IC50 of 320 μg/ml and 475 μg/ml, respectively. Suramin at 300 μg/ml significantly decreased the expression of Hpa mRNA (P < 0.005) and protein (P < 0.005) in both HO-8910 PM and HeLa cells at 48 h. CONCLUSIONS: The inhibitory effect of suramin on Hpa enzyme may be due to downregulating of its expression in cancer cells. These findings confirm the importance of Hpa in tumor growth and the potential clinical application of Hpa inhibitors in the treatment of ovarian and cervical cancer.