Inhibition of several human hepatocellular carcinoma (HCC) cell lines by deferoxamine mesylate (desferrioxamine) (DFX) was evaluated and compared with growth of the cells in the absence of DFX and with the growth of human lung fibroblast (WI38) cells. PLC/PRF/5 or HepG2 maintained for 7 days in 30 (mu)M or 60 (mu)M DFX did not increase in number and by day 7 produced little or no alpha-fetoprotein (AFP). Cell growth without DFX reached confluence at day 7 and by day 7 had AFP = 30-60 ng/ml (PLC/PRF/5) and >1,000 ng/ml (HepG2) in the supernate. (Cell growth and AFP production in 3 (mu)M DFX were mildly reduced.) Titers of hepatitis B surface antigen (HBsAg) produced by the PLC/PRF/5 cells were reduced 1-2 logs in 30 AM and 60 (mu)M DFX compared to cells grown without DFX. WI-38 cells grown with 30 AM or 60 (mu)M DFX grew at 50% of the rate of WI-38 cells without DFX. DFX inhibits the growth of PLC/PRF/5 and HepG2 cells in an apparently dose-related manner (30 (mu)M or 60 (mu)M DFX arresting cell growth and AFP production) compared to reducing the growth rate of WI-38 cells. The inhibition of PLC/PRF/5 and HepG2 cells may be due, in part, to mechanisms other than iron chelation. Many additional studies have been conducted to further evaluate these observations. These have included attempts to overcome or prevent inhibition with different iron salts, and evaluating whether inhibition occurs in the same way in six other human HCC cell lines. The inhibition of HCC cell lines by deferoxamine occurred similarly in all human HCC cell lines tested, regardless of the country of origin (South Africa, United States, Japan) or the presence or absence of HBV DNA in the cell line. In no case could equimolar concentrations of iron (ferric or ferrous salts) prevent or reverse the inhibitory effect of deferoxamine.
