Antitumor effect of deferoxamine on human hepatocellular carcinoma growing in athymic nude mice

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Abstract
Background. Iron is essential for the growth of all living cells. One of the important intracellular roles for iron is in the activation of ribonucleotide reductase, the enzyme that catalyzes the first step in DNA synthesis. Thus, the intracellular iron level may serve as a regulator of cell growth. The authors tested the hypothesis that lowering body iron concentration inhibits the growth of human-derived hepatocellular carcinoma (HCC) cells by depleting these cells of iron. Deferoxamine (DFO), an iron-chelating agent, was used to lower intracellular iron level. Methods. HCC cells, PLC/PRF/5 (7 × 106 cells/ mouse), were transplanted subcutaneously into athymic nude mice. When tumors reached 200–300 μl in size, mice with comparable tumor sizes were paired; one was treated with DFO (300 mg/kg body weight/day, 5 days/ week) intraperitoneally while the other received no treatment. Results. Eight pairs of mice with HCC were observed for 5-18 weeks. Mean tumor growth rates (TGR) (mean 2 standard error) for the untreated and treated mice were 30.5 ± 3.7 μl/week and 11.9 ±1.5 μl/week. The difference was significant (P < 0.02). In the second set of studies, DFO treatment was begun when the tumor size was smaller (100–200 μl). Four pairs of mice were observed for 4-15 weeks; mean TGR for the four untreated mice was 18.1 ± 5.1 μl/week. In two mice treated with DFO, tumors regressed completely by the seventh week after initiation of treatment. The two remaining mice on DFO therapy had much slower growing tumors, with a mean TGR of 1.8 ± 0.5μpl/week. Conclusions. Thus, our results suggest that (1) reduction of intracellular iron concentration by DFO may be useful as antitumor therapy in HCC and (2) the favorable effects of DFO treatment are best seen when treatment is begun when the tumor is small.