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Zerumbone, Sesquiterpene Photochemical from Ginger, Inhibits Angiogenesis.

Park JH, Park GM, Kim JK - Korean J. Physiol. Pharmacol. (2015)

Bottom Line: Zerumbone inhibited HUVECs proliferation, migration and tubule formation, as well as angiogenic activity by rat aorta explants.In particular, zerumbone inhibited phosphorylation of vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1, which are key regulators of endothelial cell function and angiogenesis.Overall, these results suggest that zerumbone inhibits various attributes of angiogenesis, which might contribute to its reported antitumor effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Science, Catholic University of Daegu, Gyeongsan 712-702, Korea.

ABSTRACT
Here, we investigated the role of zerumbone, a natural cyclic sesquiterpene of Zingiber zerumbet Smith, on angiogenesis using human umbilical vein endothelial cells (HUVECs). Zerumbone inhibited HUVECs proliferation, migration and tubule formation, as well as angiogenic activity by rat aorta explants. In particular, zerumbone inhibited phosphorylation of vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1, which are key regulators of endothelial cell function and angiogenesis. In vivo matrigel plug assay in mice demonstrated significant decrease in vascularization and hemoglobin content in the plugs from zerumbone-treated mice, compared with control mice. Overall, these results suggest that zerumbone inhibits various attributes of angiogenesis, which might contribute to its reported antitumor effects.

No MeSH data available.


Related in: MedlinePlus

Inhibition of endothelial cell proliferation, migration, and capillary-like tubule formation by zerumbone. HUVECs were plated in 96-well plates, allowed to attach overnight, and then cultured for 24 h with indicated concentration of zerumbone. (A) The proliferation and (B) LDH releases were determined as described in the Methods section. (C) For cell migration, a monolayer of inactivated HUVECs was wounded by scratching with a 0.1 ml pipette tip, and fresh medium containing indicated concentration of zerumbone was added. After 18 h, migration of HUVECs was measured as described in the Methods section. (D) For capillary-like tubule formation, HUVECs were seeded onto matrigel-coated 48-well plates and incubated with indicated concentration of zerumbone for 18 h. Endothelial tubules were photographed and quantitated. The results are means±SEM for at least three independent experiments. ***p<0.001 versus 0 µM zerumbone-treated cells.
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Figure 2: Inhibition of endothelial cell proliferation, migration, and capillary-like tubule formation by zerumbone. HUVECs were plated in 96-well plates, allowed to attach overnight, and then cultured for 24 h with indicated concentration of zerumbone. (A) The proliferation and (B) LDH releases were determined as described in the Methods section. (C) For cell migration, a monolayer of inactivated HUVECs was wounded by scratching with a 0.1 ml pipette tip, and fresh medium containing indicated concentration of zerumbone was added. After 18 h, migration of HUVECs was measured as described in the Methods section. (D) For capillary-like tubule formation, HUVECs were seeded onto matrigel-coated 48-well plates and incubated with indicated concentration of zerumbone for 18 h. Endothelial tubules were photographed and quantitated. The results are means±SEM for at least three independent experiments. ***p<0.001 versus 0 µM zerumbone-treated cells.

Mentions: We first assessed whether zerumbone treatment affected HUVECs proliferation using the MTS assay. Treatment with zerumbone induced a dose-dependent anti-proliferative effect in HUVECs (Fig. 2A). Zerumbone treatment at >100 µM inhibited the proliferation of HUVECs. To confirm whether the anti-proliferative effect of zerumbone was due to cytotoxicity, we next measured activity of LDH, a stable enzyme in the cell cytoplasm that is rapidly released into the culture medium upon damage of the plasma membrane. As shown in Fig. 2B, zerumbone had no effect on cytotoxicity in HUVECs suggesting that the anti-proliferative activity of zerumbone on HUVECs is not due to cytotoxicity.


Zerumbone, Sesquiterpene Photochemical from Ginger, Inhibits Angiogenesis.

Park JH, Park GM, Kim JK - Korean J. Physiol. Pharmacol. (2015)

Inhibition of endothelial cell proliferation, migration, and capillary-like tubule formation by zerumbone. HUVECs were plated in 96-well plates, allowed to attach overnight, and then cultured for 24 h with indicated concentration of zerumbone. (A) The proliferation and (B) LDH releases were determined as described in the Methods section. (C) For cell migration, a monolayer of inactivated HUVECs was wounded by scratching with a 0.1 ml pipette tip, and fresh medium containing indicated concentration of zerumbone was added. After 18 h, migration of HUVECs was measured as described in the Methods section. (D) For capillary-like tubule formation, HUVECs were seeded onto matrigel-coated 48-well plates and incubated with indicated concentration of zerumbone for 18 h. Endothelial tubules were photographed and quantitated. The results are means±SEM for at least three independent experiments. ***p<0.001 versus 0 µM zerumbone-treated cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4499645&req=5

Figure 2: Inhibition of endothelial cell proliferation, migration, and capillary-like tubule formation by zerumbone. HUVECs were plated in 96-well plates, allowed to attach overnight, and then cultured for 24 h with indicated concentration of zerumbone. (A) The proliferation and (B) LDH releases were determined as described in the Methods section. (C) For cell migration, a monolayer of inactivated HUVECs was wounded by scratching with a 0.1 ml pipette tip, and fresh medium containing indicated concentration of zerumbone was added. After 18 h, migration of HUVECs was measured as described in the Methods section. (D) For capillary-like tubule formation, HUVECs were seeded onto matrigel-coated 48-well plates and incubated with indicated concentration of zerumbone for 18 h. Endothelial tubules were photographed and quantitated. The results are means±SEM for at least three independent experiments. ***p<0.001 versus 0 µM zerumbone-treated cells.
Mentions: We first assessed whether zerumbone treatment affected HUVECs proliferation using the MTS assay. Treatment with zerumbone induced a dose-dependent anti-proliferative effect in HUVECs (Fig. 2A). Zerumbone treatment at >100 µM inhibited the proliferation of HUVECs. To confirm whether the anti-proliferative effect of zerumbone was due to cytotoxicity, we next measured activity of LDH, a stable enzyme in the cell cytoplasm that is rapidly released into the culture medium upon damage of the plasma membrane. As shown in Fig. 2B, zerumbone had no effect on cytotoxicity in HUVECs suggesting that the anti-proliferative activity of zerumbone on HUVECs is not due to cytotoxicity.

Bottom Line: Zerumbone inhibited HUVECs proliferation, migration and tubule formation, as well as angiogenic activity by rat aorta explants.In particular, zerumbone inhibited phosphorylation of vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1, which are key regulators of endothelial cell function and angiogenesis.Overall, these results suggest that zerumbone inhibits various attributes of angiogenesis, which might contribute to its reported antitumor effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Science, Catholic University of Daegu, Gyeongsan 712-702, Korea.

ABSTRACT
Here, we investigated the role of zerumbone, a natural cyclic sesquiterpene of Zingiber zerumbet Smith, on angiogenesis using human umbilical vein endothelial cells (HUVECs). Zerumbone inhibited HUVECs proliferation, migration and tubule formation, as well as angiogenic activity by rat aorta explants. In particular, zerumbone inhibited phosphorylation of vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1, which are key regulators of endothelial cell function and angiogenesis. In vivo matrigel plug assay in mice demonstrated significant decrease in vascularization and hemoglobin content in the plugs from zerumbone-treated mice, compared with control mice. Overall, these results suggest that zerumbone inhibits various attributes of angiogenesis, which might contribute to its reported antitumor effects.

No MeSH data available.


Related in: MedlinePlus