YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
Regular Articles
Shikonin, Acetylshikonin, and Isobutyroylshikonin Inhibit VEGF-induced Angiogenesis and Suppress Tumor Growth in Lewis Lung Carcinoma-bearing Mice
Hyo-Jung LEEHyo-Jeong LEEVenkataraman MAGESHDongwoo NAMEun-Ok LEEKwang Seok AHNMin-Hyung JUNGKyoo-Seok AHNDae-Keun KIMJi-Young KIMSung-Hoon KIM
Author information
JOURNALS FREE ACCESS

2008 Volume 128 Issue 11 Pages 1681-1688

Details
Abstract

  Lithospermum erythrorhizon has been used for treatment of inflammatory diseases and cancer as a folk remedy. Based on the evidences that anti-inflammatory agents frequently exert antiangiogenic activity, thus we examined comparatively the antiangiogenic activities of three naphthoquinone derivatives (shikonin, acetylshikonin, and isobutyroylshikonin) isolated from the plant. Three derivatives exhibited weak cytotoxicity against human umbilical vein endothelial cells (HUVECs) with IC50 of over 20 μM. Shikonin had more specific inhibitory effects on proliferation and vascular endothelial growth factor (VEGF) production by VEGF compared with different derivatives. All of derivatives significantly suppressed the migration of VEGF treated HUVECs at different optimal concentrations. Also, shikonin and acetylshikonin significantly disrupted VEGF-induced tube formation. Furthermore, three derivatives effectively downregulated the expression of urokinase-type plasminogen activator (uPA), but not its receptor uPAR. Additionally, shikonin significantly inhibited tumor growth in LLC-bearing mice, whereas its derivatives had relatively mild effects. Taken together, our findings suggest that shikonin and its derivatives exhibit the antiangiogenic and antitumorigenic effects by suppressing proliferation and angiogenic factors.

Information related to the author
© 2008 by the PHARMACEUTICAL SOCIETY OF JAPAN
Previous article Next article
feedback
Top