In vitro study of anti-ER positive breast cancer effect and mechanism of 1,2,3,4-6-pentyl-O-galloyl-beta-d-glucose (PGG)

Abstract

Breast cancer is one of the most common malignancies and the leading cause of women's death, most of breast cancers are estrogen receptor-positive (ER⁺) breast cancer which can develop into advanced stage from early stage with treatment resistance. The purpose of this study was to investigate anti-ER⁺ breast cancer effects of 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG) and its possible mechanisms. Cell viability was analyzed by MTT assay. The cell cycle distribution and apoptosis were detected by Flow cytometry. The expressions of cell proliferation- and apoptosis-related proteins were determined by western blot and immunofluorescence staining. The results showed PGG induced cytotoxicity and decreased viability of ER⁺ breast cancer T-47D and BT-474 cells. Flow cytometry analysis revealed that cell cycle was blocked in S phase at lower dose (25 μM PGG), and G1 phase at higher dose (50 or 75 μM PGG). One of the underlying mechanisms of the anti-cancer effect exerted by PGG was owed to inhibition of the expression of HURP, an up-regulated protein in human hepatocellular carcinoma which is closely related to tumor proliferation, invasion and metastasis. PGG affected cell cycle- or apoptosis-related proteins such as cyclin D1, Bcl-2 and Bax. These data suggest that PGG exerts anti-ER⁺ breast cancer effects. In this sense, our study provides new alternative therapies to treat breast cancer.

Keywords: 1,2,3,4,6-Penta-O-galloyl-β-d-glucopyranose (PGG); Cancer prevention and control; ER positive breast cancer; HURP.