Holothurin B Isolated from Holothuria atra Inhibits Angiogenesis More Potent than Curcumin in Vitro

Document Type : Original paper

Authors

1 Department of Pharmacognosy, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

2 Department of Pharmacology and Toxicology, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

3 Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

4 Applied Physiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.

Abstract

Background and objectives: Triterpene glycosides as the most bioactive components of sea cucumbers, have been considered for their various pharmacological properties especially anticancer and anti-metastasis activities. Due to the limited information on the biological properties of holothurin B as a marine triterpene glycoside, the present study aimed to examine its effect on angiogenesis and compare it with curcumin usinghuman umbilical vein endothelial cells (HUVECs). Methods: Holothurin B was isolated from Holothuria atra and identified by NMR and Mass spectroscopic data. Cell survival was estimated using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) technique and migration of cells was assessed by Transwell test. Angiogenesis was evaluatedin vitro by tube formation assay. Results: Holothurin B reduced HUVECssurvival with IC50 value of 8.16 µg/mL. At the concentrations of 5 and 7.5 µg/mL, it significantly decreased the number of migrated cells, the average length and size of tubules, and mean number of junctions; it was more potent than curcumin. Conclusion: Holothurin B could be considered as a potent antiangiogenic constituent through suppressing endothelial cell proliferation, migration and tubulogenesis in vitro, suggesting its potential for further animal and clinical investigations.
 

Keywords


[1] Iranmanesh M, Mohebbati R, Forouzanfar F, Roshan MK, Ghorbani A, Nik MJ, Soukhtanloo M. In vivo and in vitro effects of ethanolic extract of Trigonella foenum-graecum L. seeds on proliferation, angiogenesis and tube formation of endothelial cells. Res Pharm Sci. 2018; 13(4): 343–352.
[2] Bielenberg DR, Zetter BR. The contribution of angiogenesis to the process of metastasis. Cancer J. 2015; 21(4): 267–273.
[3] Tehranifard A, Rahimibashar MR. Description a sea cucumber spesies Holothuria atra Jaeger, 1833 from Kish Island Iran (Echinodermata: Holothuridea). J Basic Appl Sci Res. 2012; 2(12): 12660–12664.
[4] Grauso L, Yegdaneh A, Sharifi M, Mangoni A, Zolfaghari B, Lanzotti V. Molecular networking-based analysis of cytotoxic saponins from sea cucumber Holothuria atraMar Drugs. 2019; 17(2): 1–13.
[5] Dhinakaran DI, Lipton AP. Bioactive compounds from Holothuria atra of Indian Ocean. Springer Plus. 2014; 3(1): 1–10.
[6] Shahinozzaman M, Ishii T, Takano R, Halim MA, Hossain MA, Tawata S. Cytotoxic desulfated saponin from Holothuria atra predicted to have high binding affinity to the oncogenic kinase PAK1: a combined in vitro and in silico study. Sci Pharm. 2018; 86(3): 1–13.
[7] Zhao Q, Xue Y, Liu ZD, Li H, Wang JF, Li ZJ, Wang YM, Dong P, Xue CH. Differential effects of sulfated triterpene glycosides, holothurin A1, and 24-dehydroechinoside A, on antimetastasic activity via regulation of the MMP-9 signal pathway. J Food Sci. 2010; 75(9): 280–288.
[8] Zhao Q, Xue C, Zhang X, Dong P, Wang Y, Wang J. Antiangiogenesis effect of holothurin A1 and 24-dehydroechinoside A from Pearsonothuria graeffei. Chin Pharmacol Bull. 2011; 27(7): 934–939.
[9] Singh N, Kumar R, Gupta S, Dube A, Lakshmi V. Antileishmanial activity in vitro and in vivo of constituents of sea cucumber Actinopyga lecanoraParasitol Res. 2008; 103(2): 351–354. 
[10] Aminin DL, Menchinskaya ES, Pisliagin EA, Silchenko AS, Avilov S, Kalinin VI. Anticancer activity of sea cucumber triterpene glycosides. Mar Drugs. 2015; 13(3): 1202–1223.
[11] Bhandarkar SS, Arbiser JL. Curcumin as an inhibitor of angiogenesis.  Adv Exp Med Biol. 2007; 595: 185–195.
[12] Liu D, Schwimer J, Liu Z, Woltering EA, Greenway FL. Antiangiogenic effect of curcumin in pure versus in extract forms. Pharm Biol. 2008; 46(10-11): 677–682.
[13] Mansouri K, Rasoulpoor S, Daneshkhah A, Abolfathi S, Salari N, Mohammadi M, Rasoulpoor S, Shabani S. Clinical effects of curcumin in enhancing cancer therapy: a systematic review. BMC Cancer. 2020; 20(1): 1–11.
[14] Akbari V, Zafari S, Yegdaneh A. Anti-tuberculosis and cytotoxic evaluation of the seaweed Sargassum boveanum. Res Pharm Sci. 2018; 13(1): 30–37.
[15] Varshosaz J, Sadri F, Rostami M, Mirian M, Taymouri S. Synthesis of pectin-deoxycholic acid conjugate for targeted delivery of anticancer drugs in hepatocellular carcinoma. Int J Biol Macromol. 2019; 139: 665–677. 
[16] Dana N, Javanmard SH, Rafiee L. Antiangiogenic and antiproliferative effects of black pomegranate peel extract on melanoma cell line. Res Pharm Sci. 2015; 10(2): 117–124.
[17] Gotink KJ, Verheul HMW. Anti-angiogenic tyrosine kinase inhibitors: what is their mechanism of action? Angiogenesis. 2010; 13(1): 1–14.
[18] Yu S, Ye X, Huang H, Peng R, Su Z, Lian XY, Zhang Z. Bioactive sulfated saponins from sea cucumber Holothuria moebiiPlanta Med. 2015; 81(2): 152–159.
[19] Wang J, Han H, Chen X, Yi Y, Sun H. Cytotoxic and apoptosis-inducing activity of triterpene glycosides from Holothuria scabra and Cucumaria frondosa against HepG2 cells.  Mar Drugs. 2014; 12(8): 4274–4290.
[20] Yan B, Li L, Yi YH, Tang HF, Sun P, Zhang SY. Study on bioactive triterpene glycosides of sea cucumber Holothuria scabra Jaeger. Acad J Second Mil Med Univ. 2005; 26: 626–631. 
[21] Patil TD, Thakare SV. In silico evaluation of selected triterpene glycosides as a human DNA topoisomerase II alpha (α) inhibitor. Int J Pharm Pharm Sci. 2012; 4: 201–204.
[22] Manolova Y, Deneva V, Antonov L, Drakalska E, Momekova D, Lambov N. The effect of the water on the curcumin tautomerism: a quantitative approach. Spectrochim Acta A Mol Biomol Spectrosc.2014; 132: 815–820.
[23] Gururaj AE, Belakavadi M, Venkatesh DA, Marmé D, Salimath BP. Molecular mechanisms of anti-angiogenic effect of curcumin. Biochem Biophys Res Commun.2002; 297(4): 934–942.