Anti-tumour and anti-metastatic actions of wogonin isolated from Scutellaria baicalensis roots through anti-lymphangiogenesis

Tumour growth and metastasis are associated with angiogenesis and lymphangiogenesis through the production of vascular endothelial growth factor (VEGF) or VEGF-C in tumours, and the phosphorylation of VEGF receptor (VEGFR)-2 or VEGFR-3 in vascular endothelial cells or lymphatic endothelial cells (LECs). Tumour-associated macrophages (TAMs) play an important role in tumour lymphangiogenesis, and consequently stimulate metastasis through the lymphatic system to lymph nodes. Yoshiyuki Kimura & Maho Sumiyoshi examined the effects of wogonin isolated from Scutellaria baicalensis roots on tumour growth and metastasis using a highly metastatic model in osteosarcoma LM8-bearing mice. Wogonin (25 and 50mg/kg, twice daily) reduced tumour growth and metastasis to the lung, liver and

kidney, angiogenesis (CD31-positive cells), lymphangiogenesis (LYVE-1-positive cells), and TAM (F4/80-positive cell) numbers in the tumors of LM8-bearing mice. Wogonin (10–100?M) also inhibited increases in IL-1? production and cyclooxygenase (COX)-2 expression induced by lipopolysaccharide in THP-1 macrophages. Wogonin had no effect on VEGF-C production in LM8 cells, or VEGFR-3 expression in human lymphatic endothelial cells (HLECs), however, it inhibited VEGF-C-induced VEGFR-3 phosphorylation in HLECs. The anti-tumour and anti-metastatic actions of wogonin may be associated with the inhibition of VEGF-C-induced lymphangiogenesis through a reduction in VEGF-C-induced VEGFR-3 phosphorylation by the inhibition of COX-2 expression and IL-1? production in TAMs. Kimura Y & Sumiyoshi M. Phytomedicine. Dec 07 2012. doi:10.1016/j.phymed.2012.10.016