Figure 4.

Ferrichrome exhibits antitumor effects in FUR SUIT-2 cells. (A) SRB assay showing dose-dependent effects of ferrichrome (IC50: 0.23 µg/ml) and 5-FU (IC50: 2.96 µg/ml) on SUIT-2 cells (n=5). (B) Combination effect of ferrichrome and 5-FU in SUIT-2 cells (n=3). (C) Ferrichrome exerted anti-tumor effects equal to or stronger than 5-FU in a mouse xenograft model (n=6). Ferrichrome and 5-FU were dissolved in PBS, and 10 mg/kg of ferrichrome, PBS or 10 mg/kg of 5-FU was administered intraperitoneally every day for 8 days to BALB/c nude mice transplanted with 1×10⁶ SUIT-2 cells. The maximum tumor volume and diameter of the transplanted tumor were 684 mm³ and 11.7 mm (PBS), 303 mm³ and 9.1 mm (5-FU), and 194 mm³ and 8.4 mm (ferrichrome), respectively. The maximum combined tumor diameters were 22.8 mm (PBS), 18.1 mm (5-FU) and 16.3 mm (ferrichrome). (D) SRB assay demonstrating that 1 µg/ml ferrichrome significantly reduced tumor cell growth in both 5-FU-sensitive and FUR SUIT-2 cells after 2 days of treatment (n=5). (E) Ferrichrome suppressed tumor progression in FUR SUIT-2 cell-transplanted mice (n=6-8). The maximum tumor volume and diameter of the transplanted tumors were 468 mm³ and 11.3 mm (PBS) and 213 mm³ and 8.2 mm (ferrichrome), respectively. The maximum combined tumor diameters were 17.6 mm (PBS) and 14.9 mm (ferrichrome). Data are presented as the mean ± SD. Data were analyzed via one-way, two-way or mixed ANOVA followed by Tukey's or Bonferroni's post hoc tests. ^*P<0.05 vs. PBS or as indicated. 5-FU, 5-fluorouracil; FUR, 5-FU-resistant; SRB, sulforhodamine B; OD, optical density.