Abstract
Background
Sea cucumber is a natural resource rich in many important pharmacological compounds. this study aimed to investigate the effect of H. leucospilota extract on the induction of cell death and and Proapoptotic Activities.
Methods and Results
H. leucospilota was collected, the methanolic extract was prepared and in vitro cytotoxicity of H. leucospilota extract in the range of 12.5, 25, 50, 100, and 200 μg/mL concentrations for 48 hours on SK-BR-3 and MCR5 cells was determined. Analysis of apoptosis and cell cycle stages were performed using flow cytometry. the expressions of several apoptotic-related proteins in SK-BR-3 cells were evaluated using Western blot analysis. ROS formation and caspase activity were determined. GC-MS (involving a multistep temperature gradient and trimethylsilyl derivatives) and phytochemical analysis were used for identification of bioactive compounds. Methanolic extract inhibited the proliferation of the SK-BR-3 cell line in a dose- and time-dependent manner. As it was observed, exposure of the H. leucospilota extract triggered the apoptosis of the SK-BR-3 cells, induced DNA fragmentation, and arrested the cells in G2/M phase. treatment of the methanolic extract induced the downregulation of antiapoptotic Bcl-2 protein as well as the upregulation of Bax, caspase-3, caspase-7 proteins in SK-BR-3 cells. Methanolic extract-elicited apoptosis was accompanied with the elevated level of ROS. The GC-MS and phytochemical analysis revealed 30 compounds and the extract contained alkaloids, flavonoids, steroids, terpenoids, phenols, and saponins.
Conclusions
The antiproliferative and proapoptotic activities of the tested extract suggested the pharmacologic potential of H. leucospilota. Correspondingly, further characterizations of the identified compounds are in progress.
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References
Abrahams HJG, Gielissen MFM, Schmits IC et al (2016) Risk factors, prevalence, and course of severe fatigue after breast cancer treatment: A meta-analysis involving 12 327 breast cancer survivors. Ann. Oncol
Didkowska J, Wojciechowska U, Mańczuk M, Lobaszewski J (2016) Lung cancer epidemiology: Contemporary and future challenges worldwide. Ann. Transl. Med
Gschwind A, Fischer OM, Ullrich A (2004) The discovery of receptor tyrosine kinases: Targets for cancer therapy.Nat. Rev. Cancer
Slamon DJ, Clark GM, Wong SG et al (1987) Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. https://doi.org/10.1126/science.3798106
Soomro S, Shousha S, Taylor P et al (1991) c-erbB-2 expression in different histological types of invasive breast carcinoma. J Clin Pathol. https://doi.org/10.1136/jcp.44.3.211
Bernier J, Rossier C, Horiot JC (2016) Recent advances in regional treatment of breast carcinoma. Crit. Rev. Oncol. Hematol
Polgár C, Ott OJ, Hildebrandt G et al (2017) Late side-effects and cosmetic results of accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: 5-year resul. Lancet Oncol. https://doi.org/10.1016/S1470-2045(17)30011-6
Von Minckwitz G, Procter M, De Azambuja E et al (2017) Adjuvant pertuzumab and trastuzumab in early her2-positive breast cancer. N Engl J Med. https://doi.org/10.1056/NEJMoa1703643
Marty M, Cognetti F, Maraninchi D et al (2005) Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: The M77001 study group. J Clin Oncol. https://doi.org/10.1200/JCO.2005.04.173
Piccart-Gebhart MJ, Procter M, Leyland-Jones B et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. https://doi.org/10.1056/NEJMoa052306
Moradipoodeh B, Jamalan M, Zeinali M et al (2019) In vitro and in silico anticancer activity of amygdalin on the SK-BR-3 human breast cancer cell line. Mol Biol Rep. https://doi.org/10.1007/s11033-019-05080-3
Elmallah MIY, Micheau O (2015) Marine drugs regulating apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Mar, Drugs
Wong RSY (2011) Apoptosis in cancer: From pathogenesis to treatment.J. Exp. Clin. Cancer Res
Kinghorn AD, Chin YW, Swanson SM (2009) Discovery of natural product anticancer agents from biodiverse organisms. Curr. Opin. Drug Discov. Dev
Janakiram NB, Mohammed A, Rao CV (2015) Sea cucumbers metabolites as potent anti-cancer agents. Mar Drugs 13:2909–2923
Li YX, Himaya SWA, Kim SK (2013) Triterpenoids of marine origin as anti-cancer agents. Molecules
Aminin DL, Menchinskaya ES, Pisliagin EA et al (2015) Anticancer activity of sea cucumber triterpene glycosides. Mar, Drugs
Atashrazm F, Lowenthal RM, Woods GM et al (2015) Fucoidan and cancer: A multifunctional molecule with anti-tumor potential. Mar, Drugs
Pomin VH (2012) Fucanomics and galactanomics: Marine distribution, medicinal impact, conceptions, and challenges. Mar. Drugs
Wargasetia TL, Widodo (2017) Mechanisms of cancer cell killing by sea cucumber-derived compounds. Invest, New Drugs
Sugawara T, Zaima N, Yamamoto A et al (2006) Isolation of sphingoid bases of sea cucumber cerebrosides and their cytotoxicity against human colon cancer cells. Biosci Biotechnol Biochem. https://doi.org/10.1271/bbb.60318
Wang XH, Zou ZR, Yi YH et al (2014) Variegatusides: New non-sulphated triterpene glycosides from the sea cucumber Stichopus variegates semper. Mar Drugs. https://doi.org/10.3390/md12042004
Pomin VH (2015) Marine non-glycosaminoglycan sulfated glycans as potential pharmaceuticals. Pharmaceuticals
Zhang SL, Ling-Li, Yi YH et al (2004) Philinopgenin A, B, and C, three new triterpenoid aglycones from the sea cucumber pentacta quadrangulasis. Mar Drugs. https://doi.org/10.3390/md204185
Al Marzouqi N, Iratni R, Nemmar A et al (2011) Frondoside A inhibits human breast cancer cell survival, migration, invasion and the growth of breast tumor xenografts. Eur J Pharmacol. https://doi.org/10.1016/j.ejphar.2011.06.023
Li X, Roginsky AB, Ding XZ et al (2008) Review of the apoptosis pathways in pancreatic cancer and the anti-apoptotic effects of the novel sea cucumber compound, frondoside A. In: Annals of the New York Academy of Sciences
Seydi E, Motallebi A, Dastbaz M et al (2015) Selective toxicity of persian Gulf sea cucumber (Holothuria parva) and sponge (Haliclona oculata) methanolic extracts on liver mitochondria isolated from an animal model of hepatocellular carcinoma. Hepat Mon. https://doi.org/10.5812/hepatmon.33073
Ali S, Khan MR, Sajid M, Zahra Z (2018) Phytochemical investigation and antimicrobial appraisal of Parrotiopsis jacquemontiana (Decne) Rehder. BMC Complement Altern Med 18:1–15. https://doi.org/10.1186/s12906-018-2114-z
Brittonia PR- 1990 undefined Phytochemical Methods: A Guide to Modern Techniques of Plant Analysis.Springer
Nedeltcheva-Antonova D, Stoicheva P, Antonov L (2017) Chemical profiling of Bulgarian rose absolute (Rosa damascena Mill.) using gas chromatography–mass spectrometry and trimethylsilyl derivatives. Ind Crops Prod. https://doi.org/10.1016/j.indcrop.2017.06.007
Tantengco OAG, Jacinto SD (2015) Cytotoxic activity of crude extracts and fractions from Premna odorata (Blanco), Artocarpus camansi (Blanco) and Gliricidia sepium (Jacq.) against selected human cancer cell lines. Asian Pac J Trop Biomed 5:1037–1041.
Correia-da-Silva M, Sousa E, Pinto MMM, Kijjoa A (2017) Anticancer and cancer preventive compounds from edible marine organisms. Semin Cancer Biol 46:55–64. https://doi.org/10.1016/j.semcancer.2017.03.011
Dang NH, Thanh N, Van KP, Van et al (2007) Two new triterpene glycosides from the Vietnamese sea cucumber Holothuria scabra. Arch Pharm Res 30:1387–1391.
Fitton JH, Stringer DN, Karpiniec SS (2015) Therapies from fucoidan: An update. Mar Drugs 13:5920–5946
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Masoud mahdavinia and Mostafa Khaledi constructed the research question, Bahman Moradipoodeh, Rahim Moradi, Mostafa Khaledi, and Maryam Abedini Baghbadorani constructed the research method, collected the biological material. Mostafa Khaledi, Bahman Moradipoodeh analyzed the data, wrote and approved the final text. Masoud mahdavinia analyzed the data, wrote and approved the final text.
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The authors declare no conflict of interest. This project was supported by Ahvaz Jondishapur University of Medical Sciences(TRC-9903).
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Institutional Ethics Committee of Ahvaz Jondishapur University of Medical Sciences approved the experimental protocol (Ethics Approval Code: IR.AJUMS.REC.1399.094).
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Khaledi, M., Moradipoodeh, B., Moradi, R. et al. Antiproliferative and proapoptotic activities of Sea Cucumber H. Leucospilota extract on breast carcinoma cell line (SK-BR-3). Mol Biol Rep 49, 1191–1200 (2022). https://doi.org/10.1007/s11033-021-06947-0
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DOI: https://doi.org/10.1007/s11033-021-06947-0