Metastatic Inhibitory and Radical Scavenging Efficacies of Saponins Extracted from the Brittle Star (Ophiocoma erinaceus)

  • Amini, Elaheh (Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University) ;
  • Nabiuni, Mohammad (Department of Cell and Developmental Biology, Kharazmi University) ;
  • Baharara, Javad (Department of Animal Biology, School of Basic Science, Science and Research Branch, Islamic Azad University) ;
  • Parivar, Kazem (Department of Biology, Research Center for Applied Biology, Mashhad Branch, Islamic Azad University) ;
  • Asili, Javad (Department of Pharmacognosy, School of Pharmacy, Biotechnology Research Center, Mashhad University of Medical Sciences)
  • Published : 2015.06.26


Echinodermata use saponins in chemical defense against pathogens and predators. The molecular mechanisms of antimetastatic effects of brittle star saponins are still unknown. The present study examined antioxidant capacity and invasive ability in HeLa carcinoma cells exposed to brittle star crude saponins. Discolorating methods with DPPH and ABTS and expression of SOD-2 with RT-PCR were used to estimate the antioxidant activity. The anti-invasive activity of extracted saponins was examined through adhesion of HeLa cells to extracellular matrix, wound healing and evaluation of the mRNA levels of MMP-2 and MMP-9 by real time-PCR. The results showed that extracted saponins had cytotoxicity against cervical cancer cells and ABTS and DPPH scavenging properties with $IC_{50}$ values of 604.5, $1012{\mu}g/ml$, respectively. Further, we found that, in wound healing assay, brittle star saponins could prevent invasion of HeLa cells in a concentration dependent manner. Furthermore, cell adhesion assay demonstrated blockage of cell attachment to extracellular matrix with an $IC_{50}$ concentration of $16.1{\mu}g/ml$. The significant dose dependent down regulation of MMP-2 and MMP-9 in treated cells demonstrated that isolated saponins can decline tumor metastasis in vitro. The brittle star saponins remarkably prevented cervical cancer invasion and migration associated with down regulation of matrix metalloproteinase expression. Therefore, saponins could be suggested as an anti-invasive candidate against cervical cancer and an antioxidant as well.


Echinoderm;saponins;cervical cancer;attachment;aggression;antioxidant capacity


Supported by : Kharazmi University


  1. Amini E, Nabiuni M, Baharara J, Parivar K, Asili J (2014). Hemolytic and cytotoxic effects of saponin like Persian gulf brittle star (Ophiocoma erinaceus). J Coastal Life Med, 2, 614-620.
  2. Andersson L, Bohlin L, Lorrizi M, Ricco R, et al (1989). Biological activity of saponins and saponin-like compounds from starfish and brittle stars. Toxicon, 27, 179-88.
  3. Arslan I, Celik A (2013). Saponin rich fractions (SRPs) from soapwort show antioxidant and hemolytic activity. APCBEE Procedia, 7, 103-8.
  4. Badjatia N, Satyam A, Singh P, Seth A, Sharma A (2010). Altered antioxidant status and lipid peroxidation in Indian patients with urothelial bladder carcinoma. Urol Oncol, 28, 360-7.
  5. Baharara J, Amini E (2015). Phytochemical screening, antioxidant effect and down regulation of TGF-${\beta}$ induced by ophiocoma erinaceus brittle star crude extract. Zahedan J Res Med Sci, 15, (in press).
  6. Bai L, Ding L, Jiang Sh, et al (2014). Down-regulation of $FR{\alpha}$ inhibits proliferation and promotes apoptosis of cervical cancer cells in vitro. Asian Pac J Cancer Prev, 15, 5667-72.
  7. Byambaragchaa M, Cruz J. DI, Yang SH, Hwang SG (2013). Anti-metastatic potential of ethanol extract of Saussurea involucrata against hepatic cancer in vitro. Asian Pac J Cancer Prev, 14, 5397-402.
  8. Cheok CY, Salman HAK, Sulaiman R (2014). Extraction and quantification of saponins: A review. Food Res Int, 59, 16-40.
  9. Czarkwiani A, Dylus DV, Oliveri P (2013). Expression of skeletogenic genes during arm regeneration in the brittle star Amphiura filiformis q. Gene Expression Patterns, 13, 464-72.
  10. Di Domenico, Foppoli C, Coccia R, Perluigi M (2012). Antioxidants in cervical cancer: chemopreventive and chemotherapeutic effects of polyphenols. Biochim et biophys acta, 1822, 737-47.
  11. Guerard F, Decourcelle N, Sabourin C, Floch-Laizet C, et al (2010). Recent developments of marine ingredients for food and nutraceutical applications : a review. J Sci Hal Aquat, 2, 21-27.
  12. Gupta RK, Patel AK, Shah N, et al (2014). Oxidative stress and antioxidants in disease and cancer : a review. Asian Pac J Cancer Prev, 15, 4405-9.
  13. Huang W, Zou K (2011). Cytotoxicity of a plant steroidal saponin on human lung cancer cells. Asian Pac J Cancer Prev, 12, 513-7.
  14. Hu XQ, Wang YM, Wang JF, Xue Y, Li ZJ (2010). Dietary saponins of sea cucumber alleviate orotic acid-induced fatty liver in rats via PPAR a and SREBP-1c signaling. Lipids in Health Dis, 9, 1-9.
  15. Kumaraguruparan R, Subapriya R, Viswanathan P, Nagini S (2002). Tissue lipid peroxidation and antioxidant status in patients with adenocarcinoma of the breast. Clinica Chimica Acta, 325, 165-70.
  16. Lee KJ, Hwang SJ, Choi JH, Jeong HJ (2008). Saponins derived from the roots of Platycodon grandiflorum inhibit HT-1080 cell invasion and MMPs activities: Regulation of NF- j B activation via ROS signal pathway. Cancer Lett, 268, 233-43.
  17. Li J, Qiu DM, Chen SH, Cao SP, Xia XL (2014). Suppression of human breast cancer cell metastasis by coptisine in vitro. Asian Pac J Cancer Prev, 15, 5747-51.
  18. Li T, Xu WS, Wu GS, Chen XP, Wang YT, LU JJ (2014). Platycodin D induces apoptosis, and inhibits adhesion, migration and invasion in HepG2 hepatocellular carcinoma cells. Asian Pac J Cancer Prev, 15, 1745-9.
  19. Man S, Gao W, Yan Y, Liu Zh, Liu Ch (2011). Inhibition of matrix metalloproteinases related to metastasis by diosgenyl and pennogenyl saponins. J Ethnopharmacol, 137, 1221-7.
  20. Nishikawa M, Hashida M (2006). Inhibition of tumour metastasis by targeted delivery of antioxidant enzymes. Expert Opin Drug Deliv, 3, 356-69.
  21. Nourazarian AR, Kangari P & Salmaninejad A (2014). Roles of oxidative stress in the development and progression of breast cancer. Asian Pac J Cancer Prev, 15, 4745-51.
  22. Palasap A, Limpaiboon T, Boonsiri P, et al (2014). Cytotoxic effects of phytophenolics from caesalpinia mimosoides lamk on cervical carcinoma cell lines through an apoptotic pathway. Asian Pac J Cancer Prev, 15, 449-54.
  23. Podolak I, Galanty A, Sobolewska D (2010). Saponins as cytotoxic agents : a review. Phytochem Rev, 9, 425-74.
  24. Ponou BK, Teponno RB, Ricciutelli M, et al (2010). Dimeric antioxidant and cytotoxic triterpenoid saponins from Terminalia ivorensis A. Chev Phytochemistry, 71, 2108-15.
  25. Prabhu K, Bragadeeswaran S (2013). Biological properties of brittle star Ophiocnemis marmorata collected from Parangipettai , Southeast coast of India. J Microbiol Antimicrob, 5, 110-8.
  26. Pushparaj FS, Urooj A (2014). Antioxidant activity in two pearl millet (pennisetum typhoideum) cultivars as influenced by processing. Antioxidants, 3, 55-66.
  27. Roomi MW, Monterrey JC, Kalinovsky T,Rath M, Niedzwiecki A (2010). In vitro modulation of MMP-2 and MMP-9 in human cervical and ovarian cancer cell lines by cytokines , inducers and inhibitors. Oncology reports, 23, 605-14.
  28. Sharma OP, Bhat TK (2009). DPPH antioxidant assay revisited. Food Chem, 113, 1202-5.
  29. Suh SJ, Ko HK, Song KH, et al (2011). Ethylacetate fraction from Korean seaside starfish, Asterias amurensis, has an inhibitory effect on MMP-9 activity and expression and on migration behavior of TNF-${\alpha}$ induced human aortic smooth muscle cells. Toxicology in vitro, 25, 767-73.
  30. Tapondjou LA, Nyaa LBT, Tane P, et al (2011). Cytotoxic and antioxidant triterpene saponins from Butyrospermum parkii (Sapotaceae). Carbohydr Res, 346, 2699-2704.
  31. Thakur M, Melzig MF, Fuchs H, Weng A (2011). Chemistry and pharmacology of saponins: special focus on cytotoxic properties. Botanics:Targets and Ther, 1, 19-29.
  32. Wang W, Hong J, Lee CH, et al (2004). Bioactive metabolite from the brittle star Ophioplocus japonicas. Nat Prod Sci, 10, 253-61.
  33. Weng Y, Yu L, Cui J, et al (2014). Antihyperglycemic, hypolipidemic and antioxidant activities of total saponins extracted from Aralia taibaiensis in experimental type 2 diabetic rats. J Ethnopharmacol, 152, 553-60.
  34. Xu K, Liang X, Gao F, Zhong J, Liu J (2010). Antimetastatic effect of ganoderic acid T in vitro through inhibition of cancer cell invasion. Process Biochem, 45, 1261-7.
  35. Yu J, Qian H, Li Y, Wang Y, Zhang X, Liang X, Fu M, Lin Ch (2007). Arsenic trioxide ( As 2O3 ) reduces the invasive and metastatic properties of cervical cancer cells in vitro and in vivo. Gynecol Oncol, 106, 400-6.

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