Mouse Prostate Proteome Changes Induced by Oral Pentagalloylglucose Treatment Suggest Targets for Cancer Chemoprevention

J.      Zhang; K.      Nkhata; A.      A. Shaik; L.      Wang; L.      Li; Y.      Zhang; L.      A. Higgins; K.      H. Kim; J.      D. Liao; C.      Xing; S.-H.      Kim; J.      Lu

Abstract

Recent in vitro and in vivo preclinical studies have suggested that the Oriental herbal compound penta-1, 2, 3, 4, 6-O-galloyl-beta-D-glucose (PGG) is a promising chemopreventive agent for prostate cancer. Little is known of its safety for chronic chemoprevention use and virtually nothing is known of its in vivo responsive proteins in the target organ. Here we treated male C57BL/6 mice with daily oral administration of PGG at two dosages (1 and 2 mg per mouse) from 7 to 14 weeks of age and profiled proteomic patterns in the prostate with iTRAQ labeling and 2D LC-MS/MS analyses. While neither dose affected feed intake and body weight gain, the 2 mg dose (∼80-100 mg per kg) led to a minor but statistically significant decrease of the weight of prostate and thymus. For proteomic profiling, five prostates were pooled from each group for protein extraction. Proteins were denatured, reduced, alkylated and digested to peptides. The peptides were labeled with iTRAQ reagents, mixed and subjected to 2D LC-MS/MS analyses. PGG consumption suppressed the abundance of oncoproteins (e.g., fatty acid synthase, clusterin) and up-regulated that of tumor suppressor proteins (e.g., glutathione S-transferase M), signifying changes that may contribute to prostate cancer risk reduction.

Keywords: Cancer chemoprevention, iTRAQ, penta-1, 6-O-galloyl-beta-D-glucose (PGG), prostate, proteomic, tolerated dose determination, transgenic adenocarcinoma of mouse prostate, heat shock protein 5, fatty acid synthase, glutathione S-transferase mu