Reuters Health Information (2004-05-18): Suramin inhibits apoptotic liver damage in mice
Suramin inhibits apoptotic liver damage in mice
Last Updated: 2004-05-18 14:00:16 -0400 (Reuters Health)
NEW YORK (Reuters Health) - Suramin inhibits death-receptor induced apoptosis in liver and lymphoma cells and inhibits apoptotic liver damage in mice, according to a report in the May 16th advance online publication of Nature Medicine.
Suramin has previously been shown to inhibit growth factor signaling pathways in various tumors, the authors explain, suggesting that it might also influence apoptosis signaling pathways.
Dr. Peter H. Krammer from German Cancer Research Center, Heidelberg, Germany and colleagues tested the effect of suramin on apoptosis triggered by death receptors or chemotherapeutic drugs and on apoptotic liver damage in mice.
Suramin inhibited death-receptor mediated apoptosis in hepatoma (HepG2) cells and chemotherapeutic drug-induced apoptosis in T cell lymphoma (Jurkat) cells, the authors report, but not in human B lymphoblastoid (SKW6.4) cells or prostate carcinoma (LNCaP) cells.
"Because we have shown that suramin inhibits chemotherapy-induced apoptosis, the decision to use suramin as a chemotherapeutic drug should be carefully re-evaluated," the investigators caution.
Suramin had no effect on apoptosis induced by dexamethasone or gamma-irradiation, the report indicates.
Suramin also inhibited CD95-induced fulminant liver failure and TNF-mediated hepatic apoptosis in mice, the researchers note, but had no effect on necrotic cell death in a rat model of liver transplantation.
Kinetic analysis of in vitro studies suggested that suramin blocks apoptosis at the level of procaspase 8 activation and not at the mitochondrial level. Suramin also inhibited CD95 death-inducing signaling complex (DISC) activity in hepatoma and lymphoma cells.
"Therefore," the researchers explain, "the antiapoptotic effect is mediated via a combined inhibition of the DISC and initiator caspases, which may explain, in part, the cell type selectivity of suramin."
The authors conclude, "Suramin might prove to be a helpful agent with which to bridge periods after apoptotic acute liver failure involving death receptor systems, such as that caused by fulminant viral hepatitis or toxic liver damage."
Nat Med 16 May 2004;doi:10.1038/nm1049.