Abstract
Purpose: To investigate the cytotoxic activity of suramin against HepG2 human HCC cell line.
Methods: HepG2 cells were treated with 15, 30 and 45 mu M suramin. HepG2 cell proliferation was measured by MTT and lactate dehydrogenase (LDH) assays. Heparan sulfate proteoglycans (HSPGs), glucuronic acid and glucosamine levels were measured. Moreover, apoptosis was assessed by measuring caspase-8 and caspase-9 activities. The effect of suramin on HepG2 cells was compared with the same doses of a standard drug, cisplatin.
Results: Suramin blocked heparanase leading to dose-dependent increase in HSPGs and reduction in glucuronic acid and glucosamine levels. Suramin reduced HepG2 cells survival and showed cell cytotoxicity in a dose-dependent manner with LD50 45.04 mu M, compared with cisplatin (LDSO 28.9 mu M) (p<0.05). Moreover, suramin was able to increase the activity of caspase-9 but not of caspase-8.
Conclusion: Suramin possesses cytotoxic properties, which can be partially explained by its ability to inhibit heparanase and restore HSPGs. Suramin activates intrinsic apoptosis without affecting the extrinsic pathway.