Phloroglucinol Inhibits the Bioactivities of Endothelial Progenitor Cells and Suppresses Tumor Angiogenesis in LLC-Tumor-Bearing Mice

BACKGROUND: There is increasing evidence that phloroglucinol, a compound from Ecklonia cava, induces the apoptosis of cancer cells, eventually suppressing tumor angiogenesis. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.