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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 HUVECs Differentiation. Effect of KA on matrigel tube formation of endothelial cells. Cells treated with (A) 1% ethanol (B) 10 μg/ml (C) 20 μg/ml and (D) 30 μg/ml (E) 40 μg/ml and (F) 100 μg/ml suramin as a positive control (4X). (G) The Dose response relationship of KA on rat aorta assay. The inhibitory effect was found to be in dose response manner. Data was represented as mean ± SD (n = 3). ***P <0.001.
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Figure 5: Effects of KA on HUVECs Differentiation. Effect of KA on matrigel tube formation of endothelial cells. Cells treated with (A) 1% ethanol (B) 10 μg/ml (C) 20 μg/ml and (D) 30 μg/ml (E) 40 μg/ml and (F) 100 μg/ml suramin as a positive control (4X). (G) The Dose response relationship of KA on rat aorta assay. The inhibitory effect was found to be in dose response manner. Data was represented as mean ± SD (n = 3). ***P <0.001.

Mentions: In normal setting, endothelial cells will form tube-like structure networks in a matrigel matrix within 6 h. Treatment of HUVECs with KA inhibited the growth factors induced differentiation in a dose-dependent manner. At lower concentrations, KA reduced the area occupied by the network structures and incomplete and broken tubules were formed (Figure 5). At 40 μg/ml, KA completely abrogated endothelial tube formation. The IC50 value was 14.07 ± 2.74 μg/ml comparable with that of the suramin positive 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 HUVECs Differentiation. Effect of KA on matrigel tube formation of endothelial cells. Cells treated with (A) 1% ethanol (B) 10 μg/ml (C) 20 μg/ml and (D) 30 μg/ml (E) 40 μg/ml and (F) 100 μg/ml suramin as a positive control (4X). (G) The Dose response relationship of KA on rat aorta assay. The inhibitory effect was found to be in dose response manner. Data was represented as mean ± SD (n = 3). ***P <0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Effects of KA on HUVECs Differentiation. Effect of KA on matrigel tube formation of endothelial cells. Cells treated with (A) 1% ethanol (B) 10 μg/ml (C) 20 μg/ml and (D) 30 μg/ml (E) 40 μg/ml and (F) 100 μg/ml suramin as a positive control (4X). (G) The Dose response relationship of KA on rat aorta assay. The inhibitory effect was found to be in dose response manner. Data was represented as mean ± SD (n = 3). ***P <0.001.
Mentions: In normal setting, endothelial cells will form tube-like structure networks in a matrigel matrix within 6 h. Treatment of HUVECs with KA inhibited the growth factors induced differentiation in a dose-dependent manner. At lower concentrations, KA reduced the area occupied by the network structures and incomplete and broken tubules were formed (Figure 5). At 40 μg/ml, KA completely abrogated endothelial tube formation. The IC50 value was 14.07 ± 2.74 μg/ml comparable with that of the suramin positive 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