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Abstract Title:

Galbanic acid isolated from Ferula assafoetida exerts in vivo anti-tumor activity in association with anti-angiogenesis and anti-proliferation.

Abstract Source:

Pharm Res. 2011 Mar ;28(3):597-609. Epub 2010 Nov 10. PMID: 21063754

Abstract Author(s):

Kwan-Hyun Kim, Hyo-Jung Lee, Soo-Jin Jeong, Hyo-Jeong Lee, Eun-Ok Lee, Hyun-Seok Kim, Yong Zhang, Shi-Yong Ryu, Min-Ho Lee, Junxuan Lü, Sung-Hoon Kim

Article Affiliation:

Kwan-Hyun Kim

Abstract:

PURPOSE: To investigate whether galbanic acid (GBA) exerts anti-angiogenic and anti-cancer activities.

METHODS: Using human umbilical vein endothelial cell (HUVEC) model, we analyzed effects of GBA on cellular and molecular events related to angiogenesis. We tested its direct anti-proliferative action on mouse Lewis lung cancer (LLC) cells and established its in vivo anti-angiogenic and anti-tumor efficacy using LLC model.

RESULTS: GBA significantly decreased vascular endothelial growth factor (VEGF)-induced proliferation and inhibited VEGF-induced migration and tube formation of HUVECs. These effects were accompanied by decreased phosphorylation of p38-mitogen-activated protein kinase (MAPK), c-jun N-terminal kinase (JNK), and AKT, and decreased expression of VEGFR targets endothelial nitric oxide synthase (eNOS) and cyclin D1 in VEGF-treated HUVECs. GBA also decreased LLC proliferation with an apparent G2/M arrest, but did not induce apoptosis. In vivo, inclusion of GBA in Matrigel plugs reduced VEGF-induced angiogenesis in mice. Galbanic acid given by daily i.p. injection (1 mg/kg) inhibited LLC-induced angiogenesis in an intradermal inoculation model and inhibited the growth of s.c. inoculated LLC allograft in syngenic mice. Immunohistochemistry revealed decreased CD34 microvessel density index and Ki-67 proliferative index in GBA-treated tumors.

CONCLUSIONS: GBA exerts anti-cancer activity in association with anti-angiogenic and anti-proliferative actions.

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