Piceatannol (trans-3,4,3′,5′-tetrahydroxystilbene) is a polyphenol found in Rheum undulatum, grapes, red wine, and berries and has been shown to exert anticarcinogenic effects. In the present study, we determined whether oral administration of piceatannol inhibits solid tumor growth, angiogenesis, and lung metastasis of mammary cancer cells. 4T1 cells (5 x 104 cells) were injected into the mammary fat pad of syngeneic, 6-week old, female BALB/c mice. One day after, the mice were subjected to gavage for 30 days with piceatannol (0, 10, or 20 mg/kg body weight/day). Oral piceatannol treatment induced a significant reduction in the growth of solid tumors. Immunohistochemical staining of tumor tissues revealed that the expression of Ki67 (prototypic cell cycle related nuclear antigen), cyclin D1, cyclin A, cyclin-dependent kinase (CDK)4, CDK2, hypoxia-inducible factor 1, vascular endothelial growth factor, CD31 (platelet endothelial cell adhesion molecule-1) and LYVE-1 (lymphatic vessel endothelial receptor 1) was significantly decreased in the mice received 20 mg/kg piceatannol as compared to mice received vehicle. Piceatannol significantly increased the numbers of TUNEL-positive, apoptotic cells in tumor tissues, which was accompanied by increased Bax and cleaved caspase-3 expression and reduced Bcl-2 expression. Additionally, piceatannol feeding reduced the number and volume of pulmonary tumor nodules, which was accompanied by reduced expression of matrix metalloproteinase-9 in lung tissues. Piceatannol induced a significant reduction in the blood levels of chemokine ligand (CXCL) 16, CXCL13 (BCA-1), interleukin-16, macrophage colony-stimulating factor, monocyte chemoattractant protein-1, triggering receptor expressed on myeloid cells-1, stromal cell-derived factor-1, and plasminogen activator inhibitor-1 compared to the vehicle-fed mice. The present results indicate that piceatannol has an ability to inhibit breast cancer development and metastasis and this effect is attributable to its ability to inhibit tumor angiogenesis, lymphangiogenesis and reduce the blood levels of a broad variety of cytokines and chemokines.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 606. doi:1538-7445.AM2012-606

©2012 American Association for Cancer Research
2012