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 Lu, Sung Hoon Kim

Research output: Contribution to journalArticle

32 Citations (Scopus)

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 1 2011

Fingerprint

Ferula
Tumors
Association reactions
Lung Neoplasms
Vascular Endothelial Growth Factor A
Neoplasms
Phosphorylation
galbanic acid
JNK Mitogen-Activated Protein Kinases
Nitric Oxide Synthase Type III
Cyclin D1
Endothelial cells
Human Umbilical Vein Endothelial Cells
p38 Mitogen-Activated Protein Kinases
Microvessels
Allografts
Immunohistochemistry
Cells
Apoptosis

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Cite this

Kim, Kwan Hyun ; Lee, Hyo Jung ; Jeong, Soo Jin ; Lee, Hyo Jeong ; Lee, Eun Ok ; Kim, Hyun Seok ; Zhang, Yong ; Ryu, Shi Yong ; Lee, Min Ho ; Lu, Junxuan ; Kim, Sung Hoon. / Galbanic acid isolated from Ferula assafoetida exerts in vivo anti-tumor activity in association with anti-angiogenesis and anti-proliferation. In: Pharmaceutical Research. 2011 ; Vol. 28, No. 3. pp. 597-609.
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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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Galbanic acid isolated from Ferula assafoetida exerts in vivo anti-tumor activity in association with anti-angiogenesis and anti-proliferation. / Kim, Kwan Hyun; Lee, Hyo Jung; Jeong, Soo Jin; Lee, Hyo Jeong; Lee, Eun Ok; Kim, Hyun Seok; Zhang, Yong; Ryu, Shi Yong; Lee, Min Ho; Lu, Junxuan; Kim, Sung Hoon.

In: Pharmaceutical Research, Vol. 28, No. 3, 01.03.2011, p. 597-609.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Galbanic acid isolated from Ferula assafoetida exerts in vivo anti-tumor activity in association with anti-angiogenesis and anti-proliferation

AU - Kim, Kwan Hyun

AU - Lee, Hyo Jung

AU - Jeong, Soo Jin

AU - Lee, Hyo Jeong

AU - Lee, Eun Ok

AU - Kim, Hyun Seok

AU - Zhang, Yong

AU - Ryu, Shi Yong

AU - Lee, Min Ho

AU - Lu, Junxuan

AU - Kim, Sung Hoon

PY - 2011/3/1

Y1 - 2011/3/1

N2 - 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.

AB - 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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