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Antiangiogenic properties of Koetjapic acid, a natural triterpene isolated from Sandoricum koetjaoe Merr.

Nassar ZD, Aisha AF, Ahamed MB, Ismail Z, Abu-Salah KM, Alrokayan SA, Abdul Majid AM - Cancer Cell Int. (2011)

Bottom Line: Treatment with 10-50 μg/ml KA resulted in dose dependent inhibition of new blood vessels growth in ex vivo rat aortic ring assay.KA was found to be non-cytotoxic against HUVECs with IC50 40.97 ± 0.37 μg/ml.KA inhibited major angiogenesis process steps, endothelial cell migration and differentiation as well as VEGF expression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Pulau Penang, Malaysia. aminmalikshah@gmail.com.

ABSTRACT

Background: Angiogenesis, the formation of new blood vessels, has become an important target in cancer therapy. Angiogenesis plays an important role in tumor growth and metastasis. Koetjapic acid (KA) is a seco-A-ring oleanene triterpene isolated from S. koetjape. The solvent extract of this plant species was shown previously to have strong antiangiogenic activity; however the active ingredient(s) that conferred the biological activity and the mode of action was not established. Given the high concentration of KA in S. koetjape, an attempt has been made in this study to investigate the antiangiogenic properties of KA.

Results: Treatment with 10-50 μg/ml KA resulted in dose dependent inhibition of new blood vessels growth in ex vivo rat aortic ring assay. KA was found to be non-cytotoxic against HUVECs with IC50 40.97 ± 0.37 μg/ml. KA inhibited major angiogenesis process steps, endothelial cell migration and differentiation as well as VEGF expression.

Conclusions: The non-cytotoxic compound, KA, may be a potent antiangiogenic agent; its activity may be attributed to inhibition of endothelial cells migration and differentiation as well VEGF suppression.

No MeSH data available.


Related in: MedlinePlus

Effects of KA on neovascularization in CAM assay. Effect of KA on neovascularization in chorioallantoic membrane of chick embryo. The embryos were treated for 24 h with (A) 1% ethanol as a negative control, (B) 50 μg/ml and (C) 100 μg/ml. The pictures were captured under dissecting microscope. Arrows indicate the place of agarose discs application. KA inhibited the neovascularisation in a dose-dependent manner by 41.8 ± 7.2% and 64.9 ± 8.7% at 50 and 100 μg respectively. Data presented in mean ± SD.
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Figure 6: Effects of KA on neovascularization in CAM assay. Effect of KA on neovascularization in chorioallantoic membrane of chick embryo. The embryos were treated for 24 h with (A) 1% ethanol as a negative control, (B) 50 μg/ml and (C) 100 μg/ml. The pictures were captured under dissecting microscope. Arrows indicate the place of agarose discs application. KA inhibited the neovascularisation in a dose-dependent manner by 41.8 ± 7.2% and 64.9 ± 8.7% at 50 and 100 μg respectively. Data presented in mean ± SD.

Mentions: Vascularisation in chick embryo was significantly inhibited by KA at 100 and 50 μg/disc. The displayed images in Figure 6 show normal vasculature pattern in the untreated CAMs with primary, secondary and tertiary vessels and dendritic branching pattern. On the other hand, the 100 and 50 μg KA-treated CAM showed distorted architecture in the vasculature. The number of the blood vessels was decreased significantly in treated CAMs. KA inhibited the formation of new blood vessels significantly by 41.8 ± 7.2% and 64.9 ± 8.7% at 50 and 100 μg respectively, when compared to the control.


Antiangiogenic properties of Koetjapic acid, a natural triterpene isolated from Sandoricum koetjaoe Merr.

Nassar ZD, Aisha AF, Ahamed MB, Ismail Z, Abu-Salah KM, Alrokayan SA, Abdul Majid AM - Cancer Cell Int. (2011)

Effects of KA on neovascularization in CAM assay. Effect of KA on neovascularization in chorioallantoic membrane of chick embryo. The embryos were treated for 24 h with (A) 1% ethanol as a negative control, (B) 50 μg/ml and (C) 100 μg/ml. The pictures were captured under dissecting microscope. Arrows indicate the place of agarose discs application. KA inhibited the neovascularisation in a dose-dependent manner by 41.8 ± 7.2% and 64.9 ± 8.7% at 50 and 100 μg respectively. Data presented in mean ± SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3111336&req=5

Figure 6: Effects of KA on neovascularization in CAM assay. Effect of KA on neovascularization in chorioallantoic membrane of chick embryo. The embryos were treated for 24 h with (A) 1% ethanol as a negative control, (B) 50 μg/ml and (C) 100 μg/ml. The pictures were captured under dissecting microscope. Arrows indicate the place of agarose discs application. KA inhibited the neovascularisation in a dose-dependent manner by 41.8 ± 7.2% and 64.9 ± 8.7% at 50 and 100 μg respectively. Data presented in mean ± SD.
Mentions: Vascularisation in chick embryo was significantly inhibited by KA at 100 and 50 μg/disc. The displayed images in Figure 6 show normal vasculature pattern in the untreated CAMs with primary, secondary and tertiary vessels and dendritic branching pattern. On the other hand, the 100 and 50 μg KA-treated CAM showed distorted architecture in the vasculature. The number of the blood vessels was decreased significantly in treated CAMs. KA inhibited the formation of new blood vessels significantly by 41.8 ± 7.2% and 64.9 ± 8.7% at 50 and 100 μg respectively, when compared to the control.

Bottom Line: Treatment with 10-50 μg/ml KA resulted in dose dependent inhibition of new blood vessels growth in ex vivo rat aortic ring assay.KA was found to be non-cytotoxic against HUVECs with IC50 40.97 ± 0.37 μg/ml.KA inhibited major angiogenesis process steps, endothelial cell migration and differentiation as well as VEGF expression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Pulau Penang, Malaysia. aminmalikshah@gmail.com.

ABSTRACT

Background: Angiogenesis, the formation of new blood vessels, has become an important target in cancer therapy. Angiogenesis plays an important role in tumor growth and metastasis. Koetjapic acid (KA) is a seco-A-ring oleanene triterpene isolated from S. koetjape. The solvent extract of this plant species was shown previously to have strong antiangiogenic activity; however the active ingredient(s) that conferred the biological activity and the mode of action was not established. Given the high concentration of KA in S. koetjape, an attempt has been made in this study to investigate the antiangiogenic properties of KA.

Results: Treatment with 10-50 μg/ml KA resulted in dose dependent inhibition of new blood vessels growth in ex vivo rat aortic ring assay. KA was found to be non-cytotoxic against HUVECs with IC50 40.97 ± 0.37 μg/ml. KA inhibited major angiogenesis process steps, endothelial cell migration and differentiation as well as VEGF expression.

Conclusions: The non-cytotoxic compound, KA, may be a potent antiangiogenic agent; its activity may be attributed to inhibition of endothelial cells migration and differentiation as well VEGF suppression.

No MeSH data available.


Related in: MedlinePlus