Shikonin, Acetylshikonin, and Isobutyroylshikonin Inhibit VEGF-induced Angiogenesis and Suppress Tumor Growth in Lewis Lung Carcinoma-bearing Mice

Abstract

Lithospermum erythrorhizon has been used for treatment of in‰ammatory diseases and cancer as a folk remedy. Based on the evidences that anti-in‰ammatory 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 IC 50 of over 20 mM. Shikonin had more speciˆc inhibitory eŠects on proliferation and vascular endothelial growth factor (VEGF) production by VEGF compared with diŠerent derivatives. All of derivatives signiˆcantly suppressed the migration of VEGF treated HUVECs at diŠerent optimal concentrations. Also, shikonin and acetylshikonin signiˆcantly disrupted VEGF-induced tube formation. Furthermore, three derivatives eŠectively downregulated the expression of urokinase-type plasminogen activator (uPA), but not its receptor uPAR. Additionally, shikonin signiˆcantly inhibited tumor growth in LLC-bearing mice, whereas its derivatives had relatively mild eŠects. Taken together, ourˆndings suggest that shikonin and its derivatives exhibit the antiangiogenic and antitumorigenic eŠects by suppressing proliferation and angiogenic factors.

Targeting the synovial angiogenesis as a novel treatment approach to osteoarthritis

“…showed anti-angiogenic activities by inhibiting endothelial cells migration and proliferation through the inhibition of VEGF production [Lee et al 2008].…”

Compound K Inhibits Basic Fibroblast Growth Factor-Induced Angiogenesis via Regulation of p38 Mitogen Activated Protein Kinaseand AKT in Human Umbilical Vein Endothelial Cells

“…24,25) Likewise, anti-angiogenic activities by paonol, shikonin, campesterol, heyneanol A and 6-(1-oxobutyl)-5,8-dimethoxy-1,4-naphthoquinone, Korean Angelica gigas and Kamikaekyuktang, Shiquandabutangjiaweibang and Bojungbangdoktang were demonstrated by our group. [26][27][28][29][30][31][32][33] In the present study, we have investigated whether or not CK can inhibit bFGF-mediated angiogenesis and its related signaling pathways in HUVECs.…”

Encapsulation of Acetylshikonin by Polyamidoamine Dendrimers for Preparing Prominent Nanoparticles

“…In the last decade, extensive research has been conducted to study the antitumor activity and the mechanism of the antitumor effect of AS (5)(6)(7)(8)(9). However, AS exhibits extremely low solubility in water (detected in this study).…”