Phloroglucinol inhibits the bioactivities of endothelial progenitor cells and suppresses tumor angiogenesis in LLC-tumor-bearing mice

• Published in: PloS one Vol. 7; no. 4; p. e33618
• Main Authors: Kwon, Yi-Hong, Jung, Seok-Yun, Kim, Jae-Won, Lee, Sang-Hun, Lee, Jun-Hee, Lee, Boo-Yong, Kwon, Sang-Mo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.04.2012; Public Library of Science (PLoS)
• Subjects: Administration, Oral; Analysis; Angiogenesis; Angiogenesis Inhibitors - therapeutic use; Animals; Antigens; Apoptosis; Apoptosis - drug effects; Bearing; Biocompatibility; Biological activity; Biology; Biotechnology; Bone marrow; Cancer; Capillary tubes; Carcinoma, Lewis Lung - blood supply; Carcinoma, Lewis Lung - pathology; Carcinoma, Lewis Lung - prevention & control; CD34 antigen; CD45 antigen; Cell Movement - drug effects; Cells (biology); Cells, Cultured; Collagen - metabolism; Drug Combinations; Drug development; Endothelium; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Food science; Functional foods & nutraceuticals; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Indicators and Reagents - administration & dosage; Laboratories; Laminin - metabolism; Lung cancer; Lung carcinoma; Male; Medical research; Medicine; Metastasis; Mice; Mice, Inbred C57BL; Natural products; Neovascularization, Pathologic - prevention & control; Oral administration; Peripheral blood; Phloroglucinol; Phloroglucinol - administration & dosage; Physiology; Progenitor cells; Proteoglycans - metabolism; Rodents; Stem cells; Stem Cells - cytology; Stem Cells - drug effects; Stem Cells - metabolism; Toxicity; Tumorigenesis; Tumors; Umbilical cord; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Wound healing; South Korea
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0033618

There is increasing evidence that phloroglucinol, a compound from Ecklonia cava, induces the apoptosis of cancer cells, eventually suppressing tumor angiogenesis. This is the first report on phloroglucinol's ability to potentially inhibit the functional bioactivities of endothelial progenitor cells (EPCs) and thereby attenuate tumor growth and angiogenesis in the Lewis lung carcinoma (LLC)-tumor-bearing mouse model. Although Phloroglucinol did not affect their cell toxicity, it specifically inhibited vascular endothelial growth factor (VEGF) dependent migration and capillary-like tube formation of EPCs. Our matrigel plug assay clearly indicated that orally injected phloroglucinol effectively disrupts VEGF-induced neovessel formation. Moreover, we demonstrated that when phloroglucinol is orally administered, it significantly inhibits tumor growth and angiogenesis as well as CD45(-)/CD34(+) progenitor mobilization into peripheral blood in vivo in the LLC-tumor-bearing mouse model. These results suggest a novel role for Phloroglucinol: Phloroglucinol might be a modulator of circulating EPC bioactivities, eventually suppressing tumorigenesis. Therefore, phloroglucinol might be a candidate compound for biosafe drugs that target tumor angiogenesis.