Abstract
Angiogenesis plays a key role in tumor growth, invasion and metastasis of cancer diseases and therefore, the inhibition of angiogenesis can provide an important therapeutic approach in cancer diseases. This study was designed to compare the anti-angiogenic activities of the ethanolic extract of Artemisia sieberi Besser, Asteraceae, and its active substance, artemisinin in both in vitro and in vivo models. To compare cytotoxicity level of ethanolic extract of A. sieberi with artemisinin, different concentrations (1-100 μg/ml) were tested using MTT assay on human umbilical vein endothelial cells. The anti-angiogenic properties of serial concentrations of ethanolic extract of A. sieberi and artemisinin were examined on human umbilical vein endothelial cells using a three-dimensional angiogenesis assay (in vitro model) and in the chick chorioallantoic membrane assay as in vivo model. The effects of ethanolic extract of A. sieberi and artemisinin were also tested on the expression of VEGFR-1, VEGFR-2 and CD34 genes using real-time PCR. Ethanolic extract of A. sieberi and artemisinin significantly (p < 0.001) inhibited the angiogenesis in the human umbilical vein endothelial cells culture whilst the ethanolic extract of A. sieberi showed higher effect in a concentration-dependent fashion (p < 0.001). The chick chorioallantoic membrane angiogenesis was also completely inhibited by ethanolic extract of A. sieberi at concentration of 33ng/100 μl/egg. The gene expression analysis showed that the ethanolic extract of A. sieberi and artemisinin reduced the transcription of VEGFR-1, VEGFR-2 and CD34 genes in a concentration-dependent manner. This study demonstrated that the ethanolic extract of A. sieberi is strongly able to inhibit the angiogenesis in human umbilical vein endothelial cells and chick chorioallantoic membrane models compared to the artemisinin.
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ZA (PhD student) contributed by running the laboratory work, biological studies, analysis of the data and drafting the paper. SM contributed to editing of the manuscript and conducting the laboratory work. SA contributed to running the laboratory works and preparing material for analysis. HAA designed the study, supervised the laboratory work, was responsible for financial support, analysis of the data, and contributed to critical reading of the manuscript. All the authors have read the final manuscript and approved its submission.
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Abdolmaleki, Z., Arab, HA., Amanpour, S. et al. Anti-angiogenic effects of ethanolic extract of Artemisia sieberi compared to its active substance, artemisinin. Rev. Bras. Farmacogn. 26, 326–333 (2016). https://doi.org/10.1016/j.bjp.2015.11.008
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DOI: https://doi.org/10.1016/j.bjp.2015.11.008