In Silico Analysis of Sea Cucumber Bioactive Compounds as Anti-Breast Cancer Mechanism Using AutoDock Vina

Document Type : Research Paper


1 Department of Biology, FMIPA Universitas Indonesia, Kampus UI Depok, 16424, Indonesia;cResearch Cluster of Bioprospecting for Sustaining Nature, Department of Biology, FMIPA Universitas Indonesia, Kampus UI Depok, 16424, Indonesia

2 Faculty of Pharmacy, FMIPA Universitas Indonesia, Kampus UI Depok, 16424, Indonesia



In recent years, the potential of marine natural products as anticancer agents, specifically for breast cancer, has been examined. The sea cucumber (Holothuroidea: Echinodermata) is known to contain triterpene glycosides, which have shown anticancer or cytotoxic activity. In this research, molecular docking of selected sea cucumber bioactive compounds was conducted on five receptor targets that play an important role in breast cancer: estrogen receptor alpha (ER-α), fibroblast growth factor receptor 1 (FGFR1), vascular endothelial growth factor receptor 2 (VEGFR2), progesterone receptor (PR), and insulin-like growth factor 1 receptor (IGFR1). The purpose of this was to observe the interaction between active compounds and the active site of breast cancer receptor targets. Holothurin A gave the lowest binding energy (-7.1 kcal/mol) and was involved in a hydrogen bond with amino acid His-516 when superposition towards to E4D cocrystal was present. Holothurin A also had a similar posing with raloxifene, in which the hydrogen bond with His-516 with a RMSD value of 3.3 Å was observed with superposition towards to the positive control raloxifene. The analysis and visualization results of 24-dehidroechinoside that was superposed on E4D cocrystal, BMI cocrystal, and positive control raloxifene showed that 24-dehidroechinoside had a hydrophobic interaction with amino-acid residue Leu-346, a strong hydrogen bond to Gln-977, as well as a hydrogen bond to Thr-347 in a distance of 3.7 Å, and a hydrophobic interaction with amino-acid residue Ala-350. The most potent in silico anti-breast cancer compounds in sea cucumbers are holothurin A and 24-dehidroechinoside. Holothurin A is active as an anti-breast cancer agent by inhibiting ER-α, while 24-dehidroechinoside inhibits both ER-α and IGFR1.


[1] Blunt J, Copp B, Keyzers R, Munroa M, Prinsep M. Marine natural products. Nat. Prod. Rep. (2016) 33: 382-431.
[2] Gomes N, Dasari R, Chandra S, Kiss R, Kornienko A. Marine Invertebrate Metabolites with Anticancer Activities: Solutions to the “Supply Problem”. Mar. Drugs (2016) 14 (5): 98.
[3] Aminin D, Menchinskaya E, Pisliagin E, Silchenko A, Avilov S, Kalinin V. Anticancer Activity of Sea Cucumber Triterpene Glycosides. Mar. Drugs (2015)13(3): 1202-1223.
[4] Janakiram N, Mohammed A, Rao C. Sea Cucumbers Metabolites as Potent Anti-Cancer Agents. Mar. Drugs (2015) 13 (5): 2909-2923.
[5] Bordbar S, Anwar F, Saari N. High-Value Components and Bioactive from Sea Cucumbers for Functional Foods A Review. Mar. Drugs (2011) 9 (10): 1761-1805.
[6] Patil T, Thakare S. In Silico Evaluation of Selected Triterpene Glycosides as human DNA Topoisomerase II Alpha (α) Inhibitor. Int. J. Pharm. Sci. (2012) 4 (4): 201-204.
[7] Ariazi E, Ariazi J, Cordera F, Jordan V. Estrogen Receptors as Therapeutic Targets in Breast Cancer. Curr. Top Med. Chem. (2006) 6(3): 181-202.
[8] Holdman X, Welte T, Rajapakshe K, Pond A, Coarfa C, Mo Q, Huang S, Hilsenbeck S G, Edwards D P, Zhang X, Rosen J M. Upregulation of EGFR Signaling is Correlated with Tumor Stroma Remodeling and Tumor Recurrence in FGFR1-Driven Breast Cancer. Breast Cancer Res. (2015) 17: 141-149.
[9] Guo S, Colbert L, Fuller M, Zhang Y, Gonzalez-Perez R. Vascular Endothelial Growth Factor Receptor-2 in Breast Cancer. Biochim. Biophys. Acta (2010) 1806 (1): 108-121.
[10] Mohammed H, Russell IA, Stark R, Rory Stark R, Rueda OM, Theresa E. Hickey TE, Tarulli GA, Serandour AAA, Birrell SN, Bruna A, Saadi A, Menon A, Hadfield J, Pugh M, Ganesh V. Raj GV, Brown GD, D’Santos C, Robinson JLL, Silva G, Launchbury R, Perou CM, Stingl J, Caldas C, Tilley WD, Carroll JS. Progesterone Receptor Modulates Estrogen Receptor-α Action in Breast Cancer. Nature (2015) 523 (7560): 313-317.
[11] Yang Y, Yee D. Targeting Insulin and Insulin-like Growth Factor Signaling in Breast Cancer. J. Mammary Gland Biol. Neoplasia (2012) 17(3-4): 251-261.
[12] Trott, O., Olson, A. Autodock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. (2010) 31: 455-461.
[13] Zhao QXue YLiu ZDLi HWang JFLi ZJWang YMDong PXue 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: 280-288.