Figure 3.

Enhanced anti-tumor activity of fenbendazole was observed upon improvement in solubility and bioavailability. (A) Fenbendazole (FBZ) cytotoxicity in PC-3MLN4 cells is shown for drugs solubilized in either DNTC or DMSO. DNTC itself exhibits minimal cytotoxicity. FBZ-DNTC and FBZ-DMSO were significantly more cytotoxic than DNTC alone, p<0.001 for doses ≥1 µM. (B) Comparison of ED50 of FBZ when formulated in the two different vehicles, DMSO and DNTC; p<0.001. (C) Measurement of FBZ and its active metabolites (FBZ-SO and FBZ-SO₂) in the mouse plasma collected after one injection. FBZ was not detected in all samples. *, under limit of detection. (D) AT6.1 cells were inoculated intravenously 5 days prior to treatment of 100 mg/kg fenbendazole either in DMSO or DNTC, given 3 times a week until signs of morbidity were observed. Shown are Kaplan Meier survival curves of mice in each group. N=8 per group, p<0.001 in FBZ-DMSO vs. FBZ-DNTC. (E) Average of survival days for each treatment group from panel (D) Data shown are mean ± 95% confidence interval, N=8 per group, p<0.001.