Shikonin inhibits lymphangiogenesis in vitro via the modulation of cell adhesion

Lymphangiogenesis in vitro refers to the formation of new lymphatic vessels from existing ones and plays an important role in homeostasis, metabolism, and disease such as cancer metastasis to lymph node. In this study, we examined the effects of shikonin on lymphangiogenesis in vitro. First, we evaluated its effect in temperature-sensitive rat lymphatic endothelial (TR-LE) cells. A WST-8 assay indicated that shikonin induced viability of TR-LE cells. Adhesion increased in shikonin-treated TR-LE cells treated when compared to control cells. Capillary formation also decreased in the shikonin-treated TR-LE cells, with the strongest suppression seen at 4 h. However, no effects were observed on cell migration. We also tested the effect of shikonin on lymphangiogenesis in vitro in human endothelial cells (human dermal lymphatic microvascular endothelial cells, HMVEC-dLy) and observed reduced capillary formation in the shikonin-treated cells. We showed for the first time that anti-lymphangiogenetic effect of shikonin in vitro. These results suggest that shikonin may be a new drug candidate in disease such as cancer metastasis to lymph node.