Antiangiogenesis Activity Study of Awar-Awar Leaf Ethanolic Extract (Ficus Septica Burm. F.) By Chick Chorioallantoic Membrane Method
Abstract
Cancer is one of the biggest causes of death after cardiovascular disease. Furthermore, alkaloid content of awar-awar leaf extract (Ficus septica Burm. f.) is reported to exhibit cytotoxic activity in several cancer cells. This research aims to identify the antiangiogenesis activity and potential of awar-awar leaf extract (Ficus septica Burm. f.) on chorioallantoic membrane (CAM) of chicken embryo inducted with basic fibroblast growth factor (bFGF). Awar-awar leaf extract was obtained by the maceration method by using ethanol 70%. CAM was cultured in ex ovo and then angiogenesis induced by bFGF and treated by using the concentrated extract of 0.013; 0.00975; 0.0065; and 0.00325 mg/mL. From now on, the observation was done macroscopically and microscopically. Macroscopic observation result shows that an inhibition occurred at the concentration extract of 0.013 mg/mL or equal to 62.30%, 0.00975 mg/mL or equal to 51.37%, 0.0065 mg/mL or equal to 28.42%, and 0.00325 mg/mL or equal to 13.11%. Meanwhile, the microscopic observation result shows that the higher concentration of the extract, the growth of new blood vessels is decreased, demonstrated by the reduced erythrocyte density, parallel blood vessel pattern, and looser cellular density mesenchymal tissue. Moreover, the statistical analysis result shows that the increasing concentration of extract could increase the inhibition of new blood vessel growth (p <0.05). So, awar-awar leaf ethanol extract can be used as an antiangiogenesis agent in CAM of chicken embryo induced with bFGF by ex ovo.
References
Adams, R.H., Alitalo, K., 2007. Molecular regulation of angiogenesis and lymphangiogenesis. Nat. Rev. Mol. Cell Biol. 8, 464–478. https://doi.org/10.1038/nrm2183
Damu, A.G., Kuo, P.-C., Shi, L.-S., Li, C.-Y., Kuoh, C.-S., Wu, P.-L., Wu, T.-S., 2005. Phenanthroindolizidine Alkaloids from the Stems of Ficus septica. J. Nat. Prod. 68, 1071–1075. https://doi.org/10.1021/np050095o
Deryugina, E.I., Quigley, J.P., 2008. Chick embryo chorioallantoic membrane model systems to study and visualize human tumor cell metastasis. Histochem. Cell Biol. 130, 1119–1130. https://doi.org/10.1007/s00418-008-0536-2
Dewoto, H.R., 2007. Pengembangan obat tradisional Indonesia menjadi fitofarmaka. Maj. Kedokt. Indones. 57, 205–211.
Dohle, D.S., Pasa, S.D., Gustmann, S., Laub, M., Wissler, J.H., Jennissen, H.P., Dünker, N., 2009. Chick ex ovo Culture and ex ovo CAM Assay: How it Really Works. J. Vis. Exp. https://doi.org/10.3791/1620
Gamallo, J.P., Gallego, R.P., 2017. Evaluation of Antiangiogenic Property and Toxicity of Ficus septica Burm F. Stem Extracts, in: Evaluation of Antiangiogenic Property and Toxicity of Ficus Septica Burm F. Stem Extracts. Presented at the RF-ISERD International Conference, Singapore, pp. 1–17.
Goodfellow, B.S., Mikat, E.M., 2016. A stain for the simultaneous demonstration of collagen, muscle, and elastic elements in mammalian tissue. Lab. Med. 19, 243–244.
karthik, S., Djukic, T., Kim, J.-D., Zuber, B., Makanya, A., Odriozola, A., Hlushchuk, R., Filipovic, N., Jin, S.W., Djonov, V., 2018. Synergistic interaction of sprouting and intussusceptive angiogenesis during zebrafish caudal vein plexus development. Sci. Rep. 8. https://doi.org/10.1038/s41598-018-27791-6
Katsi, V.K., Psarros, C.T., Krokidis, M.G., Vamvakou, G.D., Tousoulis, D., Stefanadis, C.I., Kallikazaros, I.E., 2014. Anti-Angiogenic Therapy and Cardiovascular Diseases: Current Strategies and Future Perspectives, in: Anti-Angiogenesis Drug Discovery and Development. Elsevier, pp. 268–308. https://doi.org/10.1016/B978-0-12-803963-2.50008-9
Lansky, E.P., Paavilainen, H.M., Pawlus, A.D., Newman, R.A., 2008. Ficus spp. (fig): Ethnobotany and potential as anticancer and anti-inflammatory agents. J. Ethnopharmacol. 119, 195–213. https://doi.org/10.1016/j.jep.2008.06.025
Li, Y., Cai, B., Shen, L., Dong, Y., Lu, Q., Sun, S., Liu, S., Ma, S., Ma, P.X., Chen, J., 2017. MiRNA-29b suppresses tumor growth through simultaneously inhibiting angiogenesis and tumorigenesis by targeting Akt3. Cancer Lett. 397, 111–119.
Lokman, N.A., Elder, A.S.F., Ricciardelli, C., Oehler, M.K., 2012. Chick Chorioallantoic Membrane (CAM) Assay as an In Vivo Model to Study the Effect of Newly Identified Molecules on Ovarian Cancer Invasion and Metastasis. Int. J. Mol. Sci. 13, 9959–9970. https://doi.org/10.3390/ijms13089959
Nugroho, A.E., Hermawan, A., Putri, D.D.P., Novika, A., Meiyanto, E., 2013. Combinational effects of hexane insoluble fraction of Ficus septica Burm. F. and doxorubicin chemotherapy on T47D breast cancer cells. Asian Pac. J. Trop. Biomed. 3, 297–302. https://doi.org/10.1016/S2221-1691(13)60066-0
Oktavia, S., Wijayanti, N., Retnoaji, B., 2017. Anti-angiogenic effect of Artocarpus heterophyllus seed methanolic extract in ex ovo chicken chorioallantoic membrane. Asian Pac. J. Trop. Biomed. 7, 240–244. https://doi.org/10.1016/j.apjtb.2016.12.024
Ribatti, D., 2008. Chapter 5 Chick Embryo Chorioallantoic Membrane as a Useful Tool to Study Angiogenesis, in: International Review of Cell and Molecular Biology. Elsevier, pp. 181–224. https://doi.org/10.1016/S1937-6448(08)01405-6
Saraswati, S., Kanaujia, P.K., Kumar, S., Kumar, R., Alhaider, A.A., 2013. Tylophorine, a phenanthraindolizidine alkaloid isolated from Tylophora indica exerts antiangiogenic and antitumor activity by targeting vascular endothelial growth factor receptor 2–mediated angiogenesis. Mol. Cancer 12, 82.
Sekti, D.A., Mubarok, M.F., Armandani, I., Junedy, S., Meiyanto, E., 2010. Awar–awar (Ficus septica Burm. f.) leaves ethanolic extract induced apoptosis of MCF-7 cells by downregulation of Bcl-2. Tradit. Med. J. 15, 100–104.
Staton, C.A., Stribbling, S.M., Tazzyman, S., Hughes, R., Brown, N.J., Lewis, C.E., 2004. Current methods for assaying angiogenesis in vitro and in vivo. Int. J. Exp. Pathol. 85, 233–248.
Taiwo, B.J., Fatokun, A.A., Olubiyi, O.O., Bamigboye-Taiwo, O.T., van Heerden, F.R., Wright, C.W., 2017. Identification of compounds with cytotoxic activity from the leaf of the Nigerian medicinal plant, Anacardium occidentale L. (Anacardiaceae). Bioorg. Med. Chem. 25, 2327–2335. https://doi.org/10.1016/j.bmc.2017.02.040
Terman, B.I., Stoletov, K.V., 2001. VEGF and tumor angiogenesis. Einstein Quart J Biol Med 18, 59–66.
Ueda, J., Takagi, M., Shin-ya, K., 2009. Aminocaprophenone- and Pyrrolidine-Type Alkaloids from the Leaves of Ficus septica. J. Nat. Prod. 72, 2181–2183. https://doi.org/10.1021/np900580f
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