Pathak AK, Bhutani M, Nair AS, Ahn KS, Chakraborty A, Kadara H, Guha S, Sethi G, Aggarwal BB. EMH by inhibiting HIF-1 and VEGF (vascular endothelial growth factor) expression, but up-regulated the VHL (von Hippel-Lindau), E2F1, p53 and MDM2 gene expression. RESULTS UA reveals cytotoxicity towards several human cancer cells Several researches have been reported the cytotoxicity of UA [19C21], but it is still unclear that how UA’s anticancer activity is compared with chemotherapy drugs commonly used in clinical. We tested the antiproliferative activity of UA and six chemotherapy drugs in MDA-MB-468 and MDA-MB-231 (human breast cancer), HCT116 and SW480 (colon cancer), PC3 and DU145 (prostate cancer), MG63 and 143B (osteosarcoma). The calculated IC50 was 10 M for UA in tested lines with the exception of MG63. It was lower than 5-FU and carboplatin, and Cefoselis sulfate similar with adriamycin (ADR), camptothecin, vincristine, and paclitaxel in most cell lines (Table ?(Table1).1). Moreover, UA was demonstrated to have a time-dependent and dose-dependent manner on 4T1 and MDA-MB-231 cells (Figure ?(Figure1A).1A). It is strongly suggested that UA exhibits strong cytotoxicities (IC50 from 2 to 20 M) against a board range of human cancer cell lines. Table 1 The IC50 of UA on human cancer cell lines (M, from MTT assay, 48 h treatment) and < 0.05. Right panel: UA reduced the primary tumor size (top panel, control; bottom panel, UA group). Tumor bearing mice was treated with 20 mg/kg UA and sizes of tumors derived from 4T1 cells Cefoselis sulfate were compared after 4 weeks. UA exhibits an antiproliferative activity in breast cancer cell lines As mentioned in previous researches [22C24], UA could inhibit the breast cancer both and < 0.01). We Cefoselis sulfate subsequently conducted H&E staining of the 4T1 tumor tissue samples. The results indicated that tumor cells were slightly less proliferative in UA group but highly proliferative in control group (Figure ?(Figure2A2A). Open in a separate window Figure 2 UA inhibits tumor growth and metastasis injected with 20 mg/kg UA Cefoselis sulfate for 4 weeks and sacrificed. Tumor samples were retrieved for H&E staining. = new capillaries blood vessel in tumors. (B) Xenogen images of representative Cefoselis sulfate mouse in control group and Rabbit Polyclonal to NBPF1/9/10/12/14/15/16/20 UA group. Representative Xenogen images of the mice in 3 weeks and 4 weeks are shown. (C) UA reduced the number of lung metastasis in 4T1 tumor-bearing mice. Picture shown the number of lung metastasis sites on the lung surface for each mouse. The green line shows the average metastasis for each group. (D) Hemotoxylin & Eosin staining of lung tissues for 4T1 tumor-bearing mice and UA treated tumor-bearing mice (200 magnification). M = metastasis site. Otherwise, UA at the doses used, was not toxic to the animals as we observed no differences in animal body weights (Supplementary Figure 1C) and behaviors. Histologic examination of tissue sections (liver, kidneys, lung, spleen, brain and heart) from control and UA-treated animals also showed no detectable differences (data not shown). UA inhibits lung metastasis of 4T1 tumor bearing mice In addition to the antitumor growth effect, UA still exhibits the anti-metastasis effectiveness on 4T1 tumor bearing mice (Figure 2BC2D). 4T1 tumor bearing mice produced node metastases (Figure ?(Figure2B,2B, two -three weeks after MFP injection) and lung metastases (Figure ?(Figure2B,2B, three-four weeks after MFP injection) in five control mice whereas only two animals in UA group (20 mg/kg/2 days by injection) showed signal in the lung site (Supplementary Figure 2A). image of lung confirmed our bioluminescence results (Figure ?(Figure3A,3A, one representative animal from each group were shown). After fixation in 10% formalin solution, metastases appear as white nodules on the lung surfaces, so the number and size of visible metastatic lesions on lung surface is easy to identify. The metastasis number.