caa a22 4500 44531284X CHVBK 20180317142636.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s11095-010-0311-7 doi (NATIONALLICENCE)springer-10.1007/s11095-010-0311-7 Galbanic Acid Isolated from Ferula assafoetida Exerts In Vivo Anti-tumor Activity in Association with Anti-angiogenesis and Anti-proliferation [Elektronische Daten] [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] 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 (1mg/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. Springer Science+Business Media, LLC, 2010 angiogenesis nationallicence galbanic acid nationallicence HUVEC nationallicence Lewis lung cancer nationallicence mouse lung cancer nationallicence VEGF nationallicence Kim Kwan-Hyun College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, 130-701, Seoul, Republic of Korea aut Lee Hyo-Jung College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, 130-701, Seoul, Republic of Korea aut Jeong Soo-Jin College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, 130-701, Seoul, Republic of Korea aut Lee Hyo-Jeong College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, 130-701, Seoul, Republic of Korea aut Lee Eun-Ok College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, 130-701, Seoul, Republic of Korea aut Kim Hyun-Seok College of Medicine, Yonsei University, 120-752, Seoul, Republic of Korea aut Zhang Yong The Hormel Institute, University of Minnesota, 801 16th Avenue NE, 55912, Austin, Minnesota, USA aut Ryu Shi-Yong Korea Research Institute of Chemical Technology, Yuseong-gu, 305-600, Daejeon, Republic of Korea aut Lee Min-Ho College of Life Sciences, Kyung Hee University, 130-701, Seoul, Republic of Korea aut Lü Junxuan The Hormel Institute, University of Minnesota, 801 16th Avenue NE, 55912, Austin, Minnesota, USA aut Kim Sung-Hoon College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, 130-701, Seoul, Republic of Korea aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/3(2011-03-01), 597-609 0724-8741 28:3<597 2011 28 11095 https://doi.org/10.1007/s11095-010-0311-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0311-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kim Kwan-Hyun College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, 130-701, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Lee Hyo-Jung College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, 130-701, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Jeong Soo-Jin College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, 130-701, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Lee Hyo-Jeong College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, 130-701, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Lee Eun-Ok College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, 130-701, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Kim Hyun-Seok College of Medicine, Yonsei University, 120-752, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Zhang Yong The Hormel Institute, University of Minnesota, 801 16th Avenue NE, 55912, Austin, Minnesota, USA aut NATIONALLICENCE 700 1- Ryu Shi-Yong Korea Research Institute of Chemical Technology, Yuseong-gu, 305-600, Daejeon, Republic of Korea aut NATIONALLICENCE 700 1- Lee Min-Ho College of Life Sciences, Kyung Hee University, 130-701, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Lü Junxuan The Hormel Institute, University of Minnesota, 801 16th Avenue NE, 55912, Austin, Minnesota, USA aut NATIONALLICENCE 700 1- Kim Sung-Hoon College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, 130-701, Seoul, Republic of Korea aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/3(2011-03-01), 597-609 0724-8741 28:3<597 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer