PMID- 18817478 OWN - NLM STAT- MEDLINE DCOM- 20081216 LR - 20240324 IS - 1557-7716 (Electronic) IS - 1523-0864 (Print) IS - 1523-0864 (Linking) VI - 11 IP - 1 DP - 2009 Jan TI - Oral administration of blueberry inhibits angiogenic tumor growth and enhances survival of mice with endothelial cell neoplasm. PG - 47-58 LID - 10.1089/ars.2008.2150 [doi] AB - Endothelial cell neoplasms are the most common soft tissue tumor in infants. Subcutaneous injection of spontaneously transformed murine endothelial (EOMA) cells results in development of hemangioendothelioma (HE). We have previously shown that blueberry extract (BBE) treatment of EOMA cells in vitro prior to injection in vivo can significantly inhibit the incidence and size of developing HE. In this study, we sought to determine whether oral BBE could be effective in managing HE and to investigate the mechanisms through which BBE exerts its effects on endothelial cells. A dose-dependent decrease in HE tumor size was observed in mice receiving daily oral gavage feeds of BBE. Kaplan-Meier survival curve showed significantly enhanced survival for mice with HE tumors given BBE, compared to control. BBE treatment of EOMA cells inhibited both c-Jun N-terminal kinase (JNK) and NF-kappaB signaling pathways that culminate in monocyte chemoattractant protein-1 (MCP-1) expression required for HE development. Antiangiogenic effects of BBE on EOMA cells included decreased proliferation by BrdU assay, decreased sprouting on Matrigel, and decreased transwell migration. Thus, this work provides first evidence demonstrating that BBE can limit tumor formation through antiangiogenic effects and inhibition of JNK and NF-kappaB signaling pathways. Oral administration of BBE represents a potential therapeutic antiangiogenic strategy for treating endothelial cell neoplasms in children. FAU - Gordillo, Gayle AU - Gordillo G AD - Division of Plastic Surgery, Department of Surgery, Davis Heart Lung Research Institute, The Ohio State University, Columbus, Ohio 43210, USA. gayle.gordillo@osumc.edu FAU - Fang, Huiqing AU - Fang H FAU - Khanna, Savita AU - Khanna S FAU - Harper, Justin AU - Harper J FAU - Phillips, Gary AU - Phillips G FAU - Sen, Chandan K AU - Sen CK LA - eng GR - GM069589/GM/NIGMS NIH HHS/United States GR - K08GM066964/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Antioxid Redox Signal JT - Antioxidants & redox signaling JID - 100888899 RN - 0 (Angiogenesis Inhibitors) RN - 0 (Plant Extracts) SB - IM MH - Administration, Oral MH - Angiogenesis Inhibitors/administration & dosage/*pharmacology/therapeutic use MH - Animals MH - Blueberry Plants/chemistry MH - Cells, Cultured MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Endothelial Cells/*drug effects MH - Endothelium, Vascular/cytology MH - Female MH - Hemangioendothelioma/*drug therapy/pathology MH - Injections, Subcutaneous MH - Kaplan-Meier Estimate MH - Mice MH - Mice, Inbred Strains MH - *Phytotherapy MH - Plant Extracts/*pharmacology/standards MH - Survival Analysis MH - Tumor Burden PMC - PMC2933151 EDAT- 2008/09/27 09:00 MHDA- 2008/12/17 09:00 PMCR- 2010/01/01 CRDT- 2008/09/27 09:00 PHST- 2008/09/27 09:00 [pubmed] PHST- 2008/12/17 09:00 [medline] PHST- 2008/09/27 09:00 [entrez] PHST- 2010/01/01 00:00 [pmc-release] AID - 10.1089/ars.2008.2150 [pii] AID - 10.1089/ars.2008.2150 [doi] PST - ppublish SO - Antioxid Redox Signal. 2009 Jan;11(1):47-58. doi: 10.1089/ars.2008.2150.