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

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

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)597-609
Number of pages13
JournalPharmaceutical research
Volume28
Issue number3
DOIs
StatePublished - Mar 2011

Bibliographical note

Funding Information:
This work was supported by Medical Research Center (MRC) grant (No. 2009-0063466) (S.H. Kim) and Hormel Foundation and NIH grant CA136953 (J. Lu). All authors declare no personal or financial conflict of interests.

Keywords

  • HUVEC
  • Lewis lung cancer
  • VEGF
  • angiogenesis
  • galbanic acid
  • mouse lung cancer

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