Natural products are promising anticancer agents and antioxidants. The present study was aimed to evaluate the cytotoxic and antioxidant potential and the contents of phenolic compounds of a chloroform extract from Holothuria tubulosa collected from the Gökova Gulf (Muğla, Turkey) for the first time. Cell viability was assessed by the MTT assay. Apoptotic cell death was analyzed by flow cytometry. The antioxidant activity of the extract was determined by the DPPH radical scavenging activity assay, the ABTS radical cation scavenging activity assay, the β-carotene-linoleic acid and FRAP assays and by the phosphomolybdenum method. Total flavonoid and tannin contents in the extract were investigated. Also, the phenolic compounds of the extract were detected by HPLC. The extract showed the potential cytotoxic effect against cancer cells and was capable of inducing apoptosis in A549 and HeLa cells. Overall, the antioxidant capacity of the extract may be evaluated as low. The phenolic compound content of the extract was also found to be low. The most abundant component in the extract was ellagic acid (482.293 μg/g extract) according to the HPLC analysis. Our results may contribute to further studies on the use of H. tubulosa for obtaining new anticancer and other therapeutic agents.
This is a preview of subscription content,to check access.
Access this article
Al-Bedeary, S., Getta, H.A., and Al-Sharafi, D., The hallmarks of cancer and their therapeutic targeting in current use and clinical trials, Iraqi J. Hematol., 2020, vol. 9, pp. 1–10.
Alper, M. and Güneş, M., Evaluation of cytotoxic, apoptotic effects and phenolic compounds of sea cucumber Holothuria tubulosa (Gmelin, 1791) extracts, Turk. J. Vet. and Anim. Sci., 2020, vol. 44, pp. 641–655.
Althunibat, O.Y., Rıdzman, B.H., and Taher, M., Antioxidant and cytotoxic properties of two sea cucumber, Holothuria edulis Lesson and Stichopus horrens Selenka, Acta. Biol. Hung., 2013, vol. 64, pp. 10–20.
Amarowicz, R., Pegg, R.B., Rahimi-Moghaddam, P., et al., Free-radical scavenging capacity and antioxidant activity of selected plant species from the Canadian prairies, Food. Chem., 2004, vol. 84, pp. 551–562.
Aryal, S., Baniya, M.K., Danekhu, K., et al., Total phenolic content, flavonoid content and antioxidant potential of wild vegetables from Western Nepal, Plants (Basel), 2019, vol. 8, 96.
Athira Krishnan, K.A. and Keerthi, T. R., Analyses of methanol extracts of two marine sponges, Spongia officinalis var. ceylonensis and Sigmadocia carnosa from Southwest Coast of India for their bioactivities, Int. J. Curr. Microbiol. App. Sci., 2016, vol. 5, pp. 722–734.
Aydın, M., Türkiye denizlerinde deniz hıyarı (Holothuroidea) türleri (Sea Cucumber (Holothuroidea) Species of Turkey), Denizcilik ve Deniz Bilimleri Dergisi (Turk. J. Marit. Marine Sci.), 2016, vol. 2, pp. 49–58.
Babu, P. A., Puppala, S. S., Aswini, S. L., et al., A database of natural products and chemical entities from marine habitat, Bioinformation, 2008, vol. 3, pp. 142–143. https://doi.org/10.6026/97320630003142
Bekir, J., Mars, M., Souchard, J.P., et al., Assessment of antioxidant, anti-inflammatory, anti-cholinesterase and cytotoxic activities of pomegranate (Punica granatum) leaves, Food. Chem. Toxicol., 2013, vol. 55, pp. 470–475.
Berk, S., Tepe, B., and Arslan, S., Screening of the antioxidant, antimicrobial and DNA damage protection potentials of the aqueous extract of Asplenium ceterach DC, Afr. J. Biotechnol., 2011, vol. 10, pp. 8902–8908.
Bordbar, S., Anwar, F., and Saari, N., High-value components and bioactives from sea cucumbers for functional foods: A review, Mar. Drugs, 2011, vol. 9, pp. 1761–1805.
Castro, J. P. L., Costa, L. E. C., Pinheiro, M. P., et al., Polysaccharides of red alga Gracilaria intermedia: Structure, antioxidant activity and rheological behavior, Polímeros, 2018, vol. 28, pp. 178–186.
Cui, N., Zhang, L., Quan, M., et al., Profile of the main bioactive compounds and in vitro biological activity of different solvent extracts from Ginkgo biloba exocarp, RSC Adv., 2020, vol. 10, pp. 45105–45111.
Dhinakaran, D.I. and Lipton, A.P., Bioactive compounds from Holothuria atra of Indian ocean, SpringerPlus, 2014, vol. 3, 673.
Esmat, A.Y., Said, M.M., Soliman, A.A., et al., Bioactive compounds, antioxidant potential and hepatoprotective activity of sea cucumber (Holothuria atra) against thioacetamide intoxication in rats, Nutrition, 2012, vol. 29, pp. 258–267.
Caponio, F., Alloggio, V., and Gomes, T., Phenolic compounds of virgin olive oil: Influence of paste preparation techniques, Food Chem., 1999, vol. 64, pp. 203–209.
Hassan, I.H., Pham, H.N.T., and Nguyen T.H., Optimization of ultrasound-assisted extraction conditions formphenolics, antioxidant, and tyrosinase inhibitory activities of Vietnamese brown seaweed (Padina australis), J. Food Process. Preserv., 2021, 45, e15386.
Hayouni, E.A., Abedrabba, M., Bouix, M., et al., The effects of solvents and extraction method on the phenolic contents and biological activities in vitro of Tunisian Quercus coccifera L. and Juniperus phoenicea L. fruit extracts, Food Chem., 2007, vol. 105, pp. 1126–1134.
Janakiram, N.B., Mohammed, A., and Rao, C.V., Sea cucumbers metabolites as potent anti-cancer agents, Mar. Drugs, 2015, vol. 13, pp. 2909–2923.
Jin, H.X., Xu, H.P., Li, Y., et al., Preparation and evaluation of peptides with potential antioxidant activity by microwave assisted enzymatic hydrolysis of collagen from sea cucumber Acaudina molpadioides obtained from Zhejiang Province in China, Mar. Drugs, 2019, vol. 17, 169.
Khotimchenko, Y., Pharmacological potential of sea cucumbers, Int. J. Mol. Sci., 2018, vol. 19, 1342.
Künili, İ.E. and Çolakoģlu, F.A., Antioxidant and antimicrobial activity of sea cucumber (Holothuria tubulosa, Gmelin 1791) extracts, COMU J. Mar. Sci. Fish., 2018, vol. 1, pp. 66–71.
Lahlou, M., The success of natural products in drug discovery, Pharmacol. Pharm., 2013, vol. 4, pp. 17–31.
Li, Y.-X., Himaya, S.W.A., Kim, S.-K., Triterpenoids of marine origin as anti-cancer agents, Molecules, 2013, vol. 18, pp. 7886–7909.
Luparello, C., Ragona, D., Asaro, D.M.L., et al., Cytotoxic potential of the coelomic fluid extracted from the sea cucumber Holothuria tubulosa against triple-Negative MDA-MB231 breast cancer cells, Biology (Basel), 2019, vol. 8, 76.
Mammadov, R., Tohumlu Bitkilerde Sekonder Metabolitler, Ankara, Nobel Akademik Yayıncılık, 2014.
Mashjoor, S. and Yousefzadi, M., Cytotoxic effects of three Persian Gulf species of Holothurians, Iran J. Vet. Res., 2019, vol. 20, pp. 19–25.
Moongkarndi, P., Kosem, N., Kaslungka, S., et al., Antiproliferation, antioxidant and induction of apoptosis by Garcinia mangostana (mangosteen) on SKBR3 human breast cancer cell line, J. Ethnopharmacol., 2004, vol. 90, pp. 161–166.
Mossman, T., Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays, J. Immunol. Methods, 1983, vol. 65, pp. 55–63.
Nagle, D.G., Zhou, Y.D., Mora, F.D et al., Mechanism targeted discovery of antitumor marine natural products, Curr. Med. Chem., 2004, vol. 11, pp. 1725–1756.
Nasution, N.A., Harahap, U., Haro, G., et al., Cytotoxic activity of BornUSU I towards T47D breast cancer cells, Open Access Maced. J. Med. Sci., 2019, vol. 7, pp. 3816–3818.
Ngo, T.V., Scarlett, C.J., Bowyer, M.C., et al., Impact of different extraction solvents on bioactive compounds and antioxidant capacity from the root of Salacia chinensis L., J. Food Qual., 2017, 9305047.
Nursid, M., Marraskuranto, E., and Chasanah, E., Cytotoxicity and apoptosis induction of sea cucumber Holothuria atra extracts, Pharmacogn. Res., 2019, vol. 11, pp. 41–46.
Pangestuti, R. and Arifin, Z., Medicinal and health benefit effects of functional sea cucumbers, J. Tradit. Complement. Med., vol. 8, pp. 341–351.
Pham-Huy, L.A., He, H., and Pham-Huy, C., Free radicals, antioxidants in disease and health, Int. J. Biomed. Sci., 2008, vol. 4, pp. 89–96.
Phaniendra, A., Jestadi, D.B., and Periyasamy, L., Free radicals: Properties, sources, targets, and their implication in various diseases, Indian J. Clin. Biochem., 2015, vol. 30, pp. 11–26.
Re, R., Pellegrini, N., Proteggente, A., et al., Antioxidant activity applying an improved ABTS radical cation decolorization assay, Free Radic. Biol. Med., 1999, vol. 26, pp. 1231–1237.
Sangpairoj, K., Chaithirayanon, K., Vivithanaporn, P., et al., Extract of the sea cucumber, Holothuria scabra, induces apoptosis in human glioblastoma cell lines, Funct. Food Health. Dis., 2016, vol. 6, pp. 452–468.
Soltani, M., Parivar, K., Baharara, J., et al., Putative mechanism for apoptosis-inducing properties of crude saponin isolated from sea cucumber (Holothuria leucospilota) as an antioxidant compound, Iran J. Basic Med. Sci., 2015, vol. 18, pp. 180–187.
Sun, P., Liu, B.S., Yi, Y.H., et al., A new cytotoxic lanostane-type triterpene glycoside from the sea cucumber Holothuria impatiens, Chem. Biodivers., 2007, vol. 4, pp. 450–457.
Temel, M.K., Sitotoksik kemoterapötiklerin yirminci yüzyıldaki gelişimi, Turk. J. Oncol., 2015, vol. 30, pp. 96–108.
Truong, D-.H., Nguyen, D.H., Anh Ta, N.T., et al., Evaluation of the use of different solvents for phytochemical constituents, antioxidants, and in vitro anti-inflammatory activities of Severinia buxifolia, J. Food Qual., 2019, 8178294.
Turan, M. and Mammadov, R., Antioxidant, antimicrobial, cytotoxic, larvicidal and anthelmintic activities and phenolic contents of Cyclamen alpinum, Pharmacol. Pharm., 2018, vol. 9, pp. 100–116.
Zengin, G. and Aktümsek, A., Investigation of antioxidant potentials of solvent extracts from different anatomical parts of Asphodeline anatolica E. Tuzlacı: an endemic plant to Turkey, Afr. J. Tradit. Complement. Altern. Med., 2014, vol. 11, pp. 481–488.
Zmemlia, N., Bejaoui, S., Khemiri, I., et al., Biochemical composition and antioxidant potential of the edible Mediterranean sea cucumber Holothuria tubulosa, Grasas y Aceites, 2020, vol. 71, e364.
The authors would like to thank the Burdur Mehmet Akif Ersoy University, Scientific and the Technology Application and Research Center, for HPLC analysis and also Özgür Okur from the İzmir Institute of Technology for the help in flow cytometry analysis.
This study is a part of the master’s thesis of the first author accepted at the Department of Molecular Biology and Genetics of Muğla Sıtkı Koçman University in 2020.
Conflict of interests. The authors declare that they have no conflict of interest.
Statement on the welfare of animals. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
The article is published in the original.
About this article
Cite this article
Doğangüneş, M., Türker, A., Güneş, H. et al. Cytotoxic and Antioxidant Potential of Chloroform Extract of Holothuria tubulosa Gmelin, 1791. Russ J Mar Biol 47, 498–507 (2021). https://doi.org/10.1134/S1063074021060043