Abstract
In this study, the saponin-rich fractions of five individual (two Red and three Black) sea cucumbers (Apostichopus japonicus) in South Korea were investigated for their antiproliferative effect against HL-60, B16F10, MCF-7, and Hep3B tumor cell lines. The red sea cucumber saponin-rich fraction (SSC) from Jeju Island (JRe) decreased the growth of HL-60 with an IC50 value of 23.55 ± 3.40 μg/mL, which represented the strongest anticancer activity among the extracts. Further, SSC downregulated B-cell lymphoma extra-large (Bcl-xL), while upregulating, to different degrees, Bcl-2-associated X protein (Bax), caspase-9, caspase-3, PARP cleavage, and apoptotic bodies in cancer cells. Evidence for SSC inducing apoptosis via the mitochondria-mediated pathway was found. The contents of SSCs were determined using ultra high-performance liquid chromatography coupled with a quadrupole orbitrap mass spectrometry to comparatively evaluate the regional influence. In West Sea, the total SSC content of A. japonicus was 15.5 mg/g, representing the highest content, while A. japonicus in the South Sea yielded the lowest content at 8 mg/g. The major saponin constituent in SSC was identified as Holotoxin A1, which may the anti-tumor compound in A. japonicus.
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Aminin DL, Menchinskaya ES, Pisliagin EA, Silchenko AS, Avilov SA, Kalinin VI (2015) Anticancer activity of sea cucumber triterpene glycosides. Mar Drugs 13(3):1202–1223
Bagheri E, Hajiaghaalipour F, Nyamathulla S, Salehen N (2018) Ethanolic extract of Brucea javanica inhibit proliferation of HCT-116 colon cancer cells via caspase activation. RSC Adv 8(2):681–689
Barry MA, Behnke CA, Eastman A (1990) Activation of programmed cell death (apoptosis) by cisplatin, other anticancer drugs, toxins and hyperthermia. Biochem Pharmacol 40(10):2353–2362
Baskić D, Popović S, Ristić P, Arsenijević NN (2006) Analysis of cycloheximide-induced apoptosis in human leukocytes: fluorescence microscopy using annexin V/propidium iodide versus acridin orange/ethidium bromide. Cell Biol Int 30(11):924–932
Bordbar S, Anwar F, Saari N (2011) High-value components and bioactives from sea cucumbers for functional foods—a review. Mar Drugs 9(10):1761–1805
Chen J (2003) Overview of sea cucumber farming and sea ranching practices in China. SPC beche-de-mer Inf Bull 18:18–23
Dai Y-L, Qiao M-D, Yu P, Zheng F, Yue H, Liu S-Y (2020) Comparing eight types of ginsenosides in ginseng of different plant ages and regions using RRLC-Q-TOF MS/MS. J Ginseng Res 44(2):205–214
Dai Y-L, Jiang Y-F, Lee HG, Jeon Y-J, Kang M-C (2019) Characterization and screening of anti-tumor activity of fucoidan from acid-processed hijiki (Hizikia fusiforme). Int J Biol Macromol 139:170–180
Domon B, Costello CE (1988) A systematic nomenclature for carbohydrate fragmentations in FAB-MS/MS spectra of glycoconjugates. Glycoconj J 5(4):397–409
Fan T, Yuan W, Cong R, Yang X, Wang W, Jing Z (2009) Studies on the purification of water-soluble holothurian glycosides from Apostichopus japonicus and their tumor suppressing activity. Acta Pharm Sin 44(1):25–31
Fernando IS, Lee WW, Jayawardena TU, Kang M-C, Ann Y-S, Ko C-I et al (2018) 3β-Hydroxy-Δ5-steroidal congeners from a column fraction of Dendronephthya puetteri attenuate LPS-induced inflammatory responses in RAW 264.7 macrophages and zebrafish embryo model. RSC Adv 8(33):18626–18634
Jänicke RU, Sprengart ML, Wati MR, Porter AG (1998) Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem 273(16):9357–9360
Kabat E, Mayer M (1967) Immunological and immunochemical methodology. In: Experimental immunochemistry, chapter1, pp 22–97
Kalinin V, Aminin D, Avilov S, Silchenko A, Stonik V (2008) Studies in natural product chemistry (bioactive natural products). Elsevier Science, The Netherlands
Kan M, Kijima A (2002) Quantitative and qualitative evaluation on the color variation of the Japanese sea cucumber Stichopus japonicus. Aquac Sci 50(1):63–69
Kim S-K, Himaya S (2012) Triterpene glycosides from sea cucumbers and their biological activities. Adv Food Nutr Res 65:297–319
Kovalchuk S, Kozhemyako V, Atopkina L, Silchenko A, Avilov S, Kalinin V et al (2006) Estrogenic activity of triterpene glycosides in yeast two-hybrid assay. J Steroid Biochem Mol Biol 101(4):226–231
Li S, Wang Y, Jiang T, Wang H, Yang S, Lv Z (2016) Absorption and transport of sea cucumber saponins from Apostichopus japonicus. Mar Drugs 14(6):114
Mooney L, Al-Sakkaf K, Brown B, Dobson P (2002) Apoptotic mechanisms in T47D and MCF-7 human breast cancer cells. Br J Cancer 87(8):909–917
Nguyen BCQ, Yoshimura K, Kumazawa S, Tawata S, Maruta H (2017) Frondoside A from sea cucumber and nymphaeols from Okinawa propolis: natural anti-cancer agents that selectively inhibit PAK1 in vitro. Drug Discov Therap 11(2):110–114
Nishanthan G, Kumara P, de Croos M, Prasada D, Dissanayake D (2018) Effects of processing on proximate and fatty acid compositions of six commercial sea cucumber species of Sri Lanka. J Food Sci Technol 55(5):1933–1941
Nishimura S (1995) Guide to seashore animals of Japan with color pictures and keys, vol 2. Hoikusha, Osaka
Park S-Y, Lim HK, Lee S, Cho SK, Park S, Cho M (2011) Biological effects of various solvent fractions derived from Jeju Island red sea cucumber (Stichopus japonicus). J Korean Soc Appl Biol Chem 54(5):718–724
Salakou S, Kardamakis D, Tsamandas AC, Zolota V, Apostolakis E, Tzelepi V et al (2007) Increased Bax/Bcl-2 ratio up-regulates caspase-3 and increases apoptosis in the thymus of patients with myasthenia gravis. In Vivo 21(1):123–132
Shah VP, Midha KK, Dighe S, McGilveray IJ, Skelly JP, Yacobi A et al (1992) Analytical methods validation: bioavailability, bioequivalence, and pharmacokinetic studies. J Pharm Sci 81(3):309–312
Soltani M, Parivar K, Baharara J, Kerachian MA, Asili J (2015) Putative mechanism for apoptosis-inducing properties of crude saponin isolated from sea cucumber (Holothuria leucospilota) as an antioxidant compound. Iran J Basic Med Sci 18(2):180
Song S, Zhang L, Cao J, Xiang G, Cong P, Dong P et al (2017) Characterization of metabolic pathways and absorption of sea cucumber Saponins, Holothurin A and Echinoside A, in vitro and in vivo. J Food Sci 82(8):1961–1967
Sun X-J, Li Q, Kong L-F (2010) Comparative mitochondrial genomics within sea cucumber (Apostichopus japonicus): Provide new insights into relationships among color variants. Aquaculture 309(1):280–285
Thornberry NA, Lazebnik Y (1998) Caspases: enemies within. Science 281(5381):1312–1316
Van S, Gerbaux P, Flammang P (2010) Qualitative and quantitative saponin contents in five sea cucumbers from the Indian Ocean. Mar Drugs 8(1):173–189
Wang Z, Zhang H, Yuan W, Gong W, Tang H, Liu B et al (2012) Antifungal nortriterpene and triterpene glycosides from the sea cucumber Apostichopus japonicus Selenka. Food Chem 132(1):295–300
Weng C, Li Y, Xu D, Shi Y, Tang H (2005) Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in Jurkat leukemia T cells. J Biol Chem 280(11):10491–10500
Yang J, Wang Y, Zhang R, Jiang T, Lv Z (2015) Determination of the triterpene glycosides in sea cucumbers by liquid chromatography with evaporative light scattering and mass spectrometry detection. J Sep Sci 38(7):1117–1122
Yun S-H, Sim E-H, Han S-H, Han J-Y, Kim S-H, Silchenko AS et al (2018) Holotoxin A1 induces apoptosis by activating acid sphingomyelinase and neutral sphingomyelinase in K562 and human primary leukemia cells. Mar drugs 16(4):123
Zamora L-N, Yuan X, Carton A-G, Slater M-J (2018) Role of deposit‐feeding sea cucumbers in integrated multitrophic aquaculture: progress, problems, potential and future challenges. Rev Aquac 10(1):57–74
Zhang K, Hou H, Bu L, Li B, Xue C, Peng Z et al (2017) Effects of heat treatment on the gel properties of the body wall of sea cucumber (Apostichopus japonicus). J Food Sci Technol 54(3):707–717
Acknowledgements
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2019R1A6A1A03033553) and a research grants from the Korea Institute of Ocean Science and Technology (PE99822).
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Dai, YL., Kim, EA., Luo, HM. et al. Characterization and anti-tumor activity of saponin-rich fractions of South Korean sea cucumbers (Apostichopus japonicus). J Food Sci Technol 57, 2283–2292 (2020). https://doi.org/10.1007/s13197-020-04266-z
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DOI: https://doi.org/10.1007/s13197-020-04266-z