Discussion TNBC is the worst of all the breast malignancy subtypes, with limited treatment options due to its nature, and poor prognosis [7]. of RT-R-MDA-MB-231 cells. 2.2. ALB, FLU, FBZ, and MBZ Exhibit Anticancer Effects in an Allograft Mouse Model without Weight Loss or Hepatic and Kidney Toxicity We then examined whether the benzimidazole derivatives ALB, FLU, FBZ, and MBZ have anticancer effects on an in vivo mouse model. To determine the security of the drugs at 10 mg/kg, the drugs were orally administered once a day on a routine of 5-days-on and 2-days-off for 2 weeks. Physique 4 shows that ALB, FLU, FBZ, and MBZ did not induce any hepatic damage, as assayed by determination of plasma ALT and AST levels (Physique 4a,b); or kidney PLX8394 toxicity, as assayed by the determination of plasma creatinine levels (Physique 4c); or body weight loss (Physique 4d). The four drugs were administered to the 4T1-injected mice, and they showed no changes in body weight (Physique 4e). ALB, FLU, FBZ, and MBZ decreased Mouse monoclonal to TGF beta1 tumor volume in the 4T1-injected allograft mice model (Physique 4f), and a significant decrease in tumor volume was observed in FBZ- and MBZ-treated mice 28 days after administration (Physique 4g,h). FLU- and MBZ-treated 4T1-injected mice showed significantly decreased lung metastasis (Physique PLX8394 4i). In the RT-R-4T1-injected mouse model, FBZ and MBZ significantly decreased tumor volume (Physique 4kCm), but only MBZ showed an inhibitory effect on lung metastasis (Physique PLX8394 4n) without changes in body weight (Physique 4j). Open in a separate window Physique 4 MBZ exerts the strongest anticancer effect among the benzimidazole derivatives on 4T1 and RT-R-4T1 tumor allografts in athymic nude mice. (aCd) For the security test, the mice were divided into five groups (six mice/group) and treated with ALB, FLU, FBZ, or MBZ (10 mg/kg/mL) by oral gavage daily for 2 consecutive weeks on a routine of 5-days-on and 2-days-off. After 2 weeks, the mice were sacrificed and plasma alanine aminotransferase (ALT) (a), aspartate aminotransferase (AST) (b), and creatinine levels (c) were measured. Body weights (d) were measured three times a week for 4 weeks. The data represent the mean SD (* 0.05). (eCn) 4T1 cells or RT-R-4T1 cells (5 104 cells/100 L) were injected subcutaneously, and when tumor volumes reached 100 mm3 (2 weeks after tumor injection), mice were divided into 10 groups (= 7/each group): (1) 4T1 group, (2) 4T1 group + ALB, (3) 4T1 group + FLU, (4) 4T1 group + FBZ, (5) 4T1 group + MBZ, (6) RT-R-4T1 group, (7) RT-R-4T1 group + ALB, (8) RT-R-4T1 group + FLU, (9) RT-R-4T1 group + FBZ, (10) RT-R-4T1 group + MBZ for 2 consecutive weeks on a routine of 5-days-on and 2-days-off. Body weights (e,j) and tumor volumes (f,k) were measured three times a week from 7 days after tumor cell injection. The mice were sacrificed around the 28th day after injection, PLX8394 and tumor volumes and (g,h,l,m) lung metastasis (i,n) were measured. The data represent the PLX8394 mean SD (* 0.05; ** 0.01). 2.3. MBZ Effectively Suppresses Cell Migration and Invasion at Low Doses Because the in vivo animal study showed that of six benzimidazole derivatives tested, MBZ was most effective in decreasing tumor volume and lung metastasis without causing any toxicity, we further investigated the mechanisms underlying the anticancer effects of.