Oral administration of Pyrrolidine Dithiocarbamate (PDTC) inhibits VEGF expression, tumor angiogenesis, and growth of breast cancer in female mice

Abstract

The progression of breast cancer is associated with oxidative stress.  However, the effects of pyrrolidine dithiocarbamate (PDTC), a known 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 week old female mice (C57BL/6J) were given PDTC at 100 to 200 mg/kg/day for 3 weeks (n=10).  The control mice received regular drinking water only.  In the 2nd wk, 5x10^5 E0771 (mouse breast cancer) cells were injected in the pad of the fourth mammary gland of the mice.  Tumor size was monitored using dial calipers.  At the end of the experiment, the tumors were isolated and measured for tumor size, intratumoral microvessel (IM) density using CD31 immunohistochemistry staining, NFκB activation using EMSA, and VEGF protein levels using ELISA.  PDTC treatment caused a significant decrease in tumor weight compared to the control (0.64±0.22 vs. 1.43±0.31 g; n=8; P