Pyrrolidine Dithiocarbamate (PDTC) Treatment Reduces Tumor Growth and Angiogenesis of Breast Cancer in Female Mice

Abstract

The progression of breast cancer is associated with oxidative stress. However, the effects of pyrrolidine dithiocarbamate (PDTC), known as an antioxidant, on the development of breast cancer are poorly understood. The present study evaluates the effects of PDTC on tumor growth, the expression of vascular endothelial growth factor (VEGF), and angiogenesis of breast cancer in female mice. Eight wk old female mice (C57BL/6J) were given PDTC 50mg/50ml in drinking water for two wks. Each mouse (20 g) usually drinks 2 to 4 ml water per day. Therefore, PDTC was given around 100 to 200 mg/kg/day in mice. The control mice received regular drinking water only. 5×105 E0771 (mouse breast cancer) cells were injected near the pad of the fourth mammary gland of the mice when the experiment started. Tumor size was monitored in two perpendicular dimensions parallel with the surface of the mice using dial calipers. At the end of the experiment, the tumors were isolated for measuring tumor size, intratumoral microvessel (IM) density using CD31 immunohistochemistry staining, and VEGF protein levels using ELISA. PDTC treatment caused a significant decrease in tumor weight over the control (0.64+/−0.22 vs. 1.43+/−0.31 g; n=6; P<0.01), and a significant decrease in IM density (66.1+/−5.3 vs. 84.2+/−9.4 IM# /mm^2; P<0.05). There was a significant decrease in tissue protein levels of VEGF (22.6+/−2.1 vs. 32.4+/−2.6 pg/mg; P<0.05) in the breast tumors of mice treated with PDTC, compared to the control group. These results suggest that the antioxidant treatment with PDTC can inhibit the progression of breast cancer through the reduction of VEGF expression and angiogenesis. (NIH/HL51971 & NIH/AA013821-01A2)