Browse > Article
http://dx.doi.org/10.15188/kjopp.2022.10.36.5.175

Inhibitory Effect of the Ethanolic Seed Extract of Trichosanthes kirilowii on Angiogenesis in Human Umbilical Vein Endothelial Cells  

Shin-Hyung, Park (Department of Pathology, College of Korean Medicine, Dong-eui University)
Hyun-Ji, Park (Department of Pathology, College of Korean Medicine, Dong-eui University)
Publication Information
Journal of Physiology & Pathology in Korean Medicine / v.36, no.5, 2022 , pp. 175-180 More about this Journal
Abstract
The seeds of Trichosanthes kirilowii (STK) used in traditional Oriental medicine for the treatment of dry cough and constipation have diverse pharmacological activities, including hypolipidemic, antioxidant, immunosuppressive, and anticancer effects. However, the effect of STK on angiogenesis has not been studied yet. In this study, we investigated whether the ethanolic extract of STK (ESTK) can regulate the migration and tube formation of human umbilical vein endothelial cells (HUVECs) and explored the underlying mechanism. Results of transwell assay showed that ESTK treatment dose-dependently suppressed the migration of HUVECs. The conditioned medium collected from H1299 human lung cancer cells was used as a chemoattractant. Our observation suggests that ESTK would inhibit the recruitment of endothelial cells into tumors. In addition, ESTK treatment significantly reduced the tube formation of HUVECs. As a molecular mechanism, we found that vascular endothelial growth factor (VEGF)-induced phosphorylation of VEGF receptor 2 (VEGFR2) was completely blocked by ESTK treatment. The expression of angiogenic factors, including VEGFA, fibroblast growth factor 2 (FGF2), angiopoietin, placental growth factor (PGF), platelet derived growth factor (PDGF), angiogenin, and tumor necrosis factor (TNF)-α, was commonly decreased by ESTK treatment in H1299 cells, indicating that ESTK would reduce the production of angiogenic factors from cancer cells. Taken together, our results clearly demonstrated that ESTK exhibited anti-angiogenic effects in HUVECs, which provides another possible mechanism underlying the anticancer activities of STK.
Keywords
Seeds of Trichosanthes kirilowii; Angiogenesis; Cancer;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Nagy JA, Chang SH, Shih SC, Dvorak AM, Dvorak HF. Heterogeneity of the tumor vasculature. Semin Thromb Hemost. 2010;36:321-31.
2 Baluk P, Hashizume H, McDonald DM. Cellular abnormalities of blood vessels as targets in cancer. Curr Opin Genet Dev. 2005;15:102-11.   DOI
3 Prager GW, Poettler M. Angiogenesis in cancer. Basic mechanisms and therapeutic advances. Hamostaseologie. 2012;32(2):105-14.   DOI
4 The Jointly Published Textbook Compilation Committee of Oriental College of Medicine Nationwide Department. Herbology. Seoul: Younglim press; 2004.
5 Hou Z, Zhu L, Meng R, Wang B. Hypolipidemic and antioxidant activities of Trichosanthes kirilowii maxim seed oil and flavonoids in mice fed with a high-fat diet. J Food Biochem. 2020;44(8):e13272.   DOI
6 Hu Z, Zhou H, Zhao J, Sun J, Li M, Sun X. Microwave-assisted extraction, characterization and immunomodulatory activity on RAW264.7 cells of polysaccharides from Trichosanthes kirilowii Maxim seeds. Int J Biol Macromol. 2020;164:2861-72.   DOI
7 Park SM, Jeon SK, Kim OH, Ahn JY, Kim CH, Park SD, Lee JH. Anti-tumor effects of the ethanolic extract of Trichosanthes kirilowii seeds in colorectal cancer. Chin Med. 2019;14:43.
8 Maj E, Papiernik D, Wietrzyk J. Antiangiogenic cancer treatment: the great discovery and greater complexity (Review). Int J Oncol. 2016;49:1773-84.   DOI
9 Kendall RL, Wang G, DiSalvo J, Thomas KA. Specificity of vascular endothelial cell growth factor receptor ligand binding domains. Biochem Biophys Res Commun. 1994; 201:326-30.   DOI
10 Olsson AK, Dimberg A, Kreuger J, Claesson-Welsh L. VEGF receptor signalling - in control of vascular function. Nat Rev Mol Cell Biol. 2006;7:359-71.   DOI
11 Lamalice L, Le Boeuf F, Huot J. Endothelial cell migration during angiogenesis. Circ Res. 2007;100(6):782-94.   DOI
12 Statistics Korea. Available from: http://www.index.go.kr/ potal/main/EachDtlPageDetail.do?idx_cd=2770
13 Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-74.   DOI
14 Ogami K, Yamaguchi R, Imoto S, Tamada Y, Araki H, Print C, Miyano S. Computational gene network analysis reveals TNF-induced angiogenesis. BMC Syst Biol. 2012;6 Suppl 2(Suppl 2):S12.
15 Katoh M. FGFR inhibitors: Effects on cancer cells, tumor microenvironment and whole-body homeostasis (Review). Int J Mol Med. 2016;38(1):3-15.   DOI
16 Ostman A. PDGF receptors-mediators of autocrine tumor growth and regulators of tumor vasculature and stroma. Cytokine Growth Factor Rev. 2004;15(4):275-86.   DOI
17 Gao X, Xu Z. Mechanisms of action of angiogenin. Acta Biochim Biophys Sin (Shanghai). 2008;40(7):619-24.   DOI
18 LI X, Zhao A, Yang J, Qian J, Chen L. Study on Role of Mucin 5AC in Malignant Tumors Based on Theory of "Body Fluid" and "Phlegm and Retained Fluid". Liaoning J Trad Chin Med. 2020;8:51-4.
19 Li Y, Li D, Chen J, Wang S. A polysaccharide from Pinellia ternata inhibits cell proliferation and metastasis in human cholangiocarcinoma cells by targeting of Cdc42 and 67kDa Laminin Receptor (LR). Int J Biol Macromol. 2016;93(Pt A):520-5.   DOI
20 Hosny S, Sahyon H, Youssef M, Negm A. Prunus Armeniaca L. Seed Extract and Its Amygdalin Containing Fraction Induced Mitochondrial-Mediated Apoptosis and Autophagy in Liver Carcinogenesis. Anticancer Agents Med Chem. 2021;21(5):621-9.   DOI
21 Kim DW, Lee JH, Yoo HS, Cho JH, Lee YW, Son CH, Cho CK. Effects of Trichosanthes kirilowii Extract against Angiogenesis and Various Tumor Cells' Growth. Korean J Orient Int Med. 2008;29(2):490-9.
22 Hwang WK. Identification for TLC pattern analysis of the crude drugs (II). Ministry of Food and Drug Safety. 2013. p28
23 Zhoh CK, Uhm TY, Kim JC. Antioxidantive Effectiveness of Trichosanthes Kirilowill Maximowicz Extracts, J Korean Ind Eng Chem, Vol18, No. 6, 2007, 625-9.
24 Ye X, Ng CC, Wong JH, Ng TB, Chan GH, Guan S, et al. Ribosome-inactivating Proteins from Root Tubers and Seeds of Trichosan-thes kirilowii and Other Trichosanthes Species. Protein Pept Lett. 2016;23(8):699-706.   DOI
25 Parmar D, Apte M. Angiopoietin inhibitors: A review on targeting tumor angiogenesis. Eur J Pharmacol. 2021;899:174021.
26 Nguyen QD, De Falco S, Behar-Cohen F, Lam WC, Li X, Reichhart N, Ricci F, Pluim J, Li WW. Placental growth factor and its potential role in diabetic retinopathy and other ocular neovascular diseases. Acta Ophthalmol. 2018;96(1):e1-e9.
27 Dat NT, Jin X, Hong YS, Lee JJ. An isoaurone and other constituents from Trichosanthes kirilowii seeds inhibit hypoxia-inducible factor-1 and nuclear factor-kappaB. J Nat Prod. 2010;73(6):1167-9.   DOI
28 He D, Jin J, Zheng Y, Bruce IC, Tam S, Ma X. Anti-angiogenesis effect of trichosanthin and the underlying mechanism. Biochem Biophys Res Commun. 2013;430(2):735-40.   DOI
29 Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7-33.   DOI