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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

UHPLC-MS/MS Studies and Antiproliferative Effects in Breast Cancer Cells of Mexican Sargassum

Author(s): Fragoso-Vázquez Manuel Jonathan, Duclosel Darling, Rosales-Hernández Martha Cecilia, Estrada-Pérez Alan, Mendoza-Figueroa Humberto Lubriel, Olivares-Corichi Ivonne, Mendieta-Wejebe Jessica Elena, Reyes-López Cesar Augusto, Velasco-Quijano Jessica Sayuri, Gil-Ruiz Luis Angel and Correa-Basurto José*

Volume 23, Issue 1, 2023

Published on: 27 August, 2022

Page: [76 - 86] Pages: 11

DOI: 10.2174/1871520622666220412125740

Price: $65

Abstract

Background: Sargassum is a marine organism that, under specific conditions, drastically increases its population damaging the environment and risking other organisms. However, sargassum could represent a source of bioactive compounds to treat different diseases such as cancer. Thus, aqueous, ethanolic, and ethyl acetate extracts of sargassum from Playa del Carmen, Mexico, were subjected to metabolomic and antiproliferative assays in breast cancer cells.

Objective: To evaluate the biological effect of different extracts of sargassum, its toxicity over Artemia salina and its antiproliferative effect tested in MCF-7, MDA-MB-231, and NIH3T3 cell lines. Finally, using UHPLC-MS/MS to identify the metabolites in each extract to correlate them with its antiproliferative effect.

Methods: The sargassum sample collection was carried out in September at three different points in Playa del Carmen, Quintana Roo, Mexico. The aqueous, ethanolic, and ethyl acetate extracts of Mexican sargassum were obtained by evaporation of solvent and lyophilization. Then, these extracts were evaluated in the cytotoxicity bioassay of Artemia salina. Next, its antiproliferative effect was assessed in MCF-7, MDA-MB-231, and NIH3T3 cell lines. Using UHPLC-MS/MS, the metabolites present in each extract were identified. Finally, docking studies on sphingosine kinase 1 (PDB ID: 3VZB) of sphingosine were carried out.

Results: The extracts from sargassum showed a greater effect in the antiproliferative assays in cells than in cytotoxic assays in Artemia salina. The ethanolic extract obtained from sargassum showed the best antiproliferative activity in MCF7 and MDA-MB-231 cells. Despite its antiproliferative effect on NIH3T3 cells, an additional extract is required indicating that this extract has compounds that could have a better effect on cancer cells in fibroblast (NIH3T3). The UHPLC-MS/MS of ethanolic and the ethyl acetate extract showed that these extracts have compounds such as sphinganine C16, N, N-Dimethylsphingosine compound, and that it could be possible that the effect observed is due to their metabolites which could be ligands for the sphingosine kinase 1 as demonstrated by docking studies.

Conclusion: The ethanolic extract obtained from sargassum has better antiproliferative activity, despite not having a cytotoxic effect in Artemia salina. The antiproliferative effect could be related to the sphinganine C16, N,NDimethylphingosine identified with more abundance by UHPLC-MS/MS. In addition, these metabolites could be targets of sphingosine kinase 1.

Keywords: Sargassum, metabolomic analysis, cytotoxic, breast cancer, UHPLC-MS/MS, anticancer.

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[1]
Khalifa, S.A.M.; Shedid, E.S.; Saied, E.M.; Jassbi, A.R.; Jamebozorgi, F.H.; Rateb, M.E.; Du, M.; Abdel-Daim, M.M.; Kai, G.Y.; Al-Hammady, M.A.M.; Xiao, J.; Guo, Z.; El-Seedi, H.R. Cyanobacteria-from the oceans to the potential biotechnological and biomedical applications. Mar. Drugs, 2021, 19(5), 241.
[http://dx.doi.org/10.3390/md19050241] [PMID: 33923369]
[2]
Blunt, J.W.; Copp, B.R.; Keyzers, R.A.; Munro, M.H.G.; Prinsep, M.R. Marine natural products. Nat. Prod. Rep., 2014, 31(2), 160-258.
[http://dx.doi.org/10.1039/c3np70117d] [PMID: 24389707]
[3]
Máximo, P.; Ferreira, L.M.; Branco, P.; Lima, P.; Lourenço, A. Secondary metabolites and biological activity of invasive macroalgae of Southern Europe. Mar. Drugs, 2018, 16(8), 265.
[http://dx.doi.org/10.3390/md16080265] [PMID: 30072602]
[4]
Liu, L.; Heinrich, M.; Myers, S.; Dworjanyn, S.A. Towards a better understanding of medicinal uses of the brown seaweed Sargassum in Traditional Chinese Medicine: A phytochemical and pharmacological review. J. Ethnopharmacol., 2012, 142(3), 591-619.
[http://dx.doi.org/10.1016/j.jep.2012.05.046] [PMID: 22683660]
[5]
Khalifa, S.A.M.; Elias, N.; Farag, M.A.; Chen, L.; Saeed, A.; Hegazy, M.F.; Moustafa, M.S.; Abd El-Wahed, A.; Al-Mousawi, S.M.; Musharraf, S.G.; Chang, F.R.; Iwasaki, A.; Suenaga, K.; Alajlani, M.; Göransson, U.; El-Seedi, H.R. Marine natural products: A source of novel anticancer drugs. Mar. Drugs, 2019, 17(9), 491.
[http://dx.doi.org/10.3390/md17090491] [PMID: 31443597]
[6]
Khalaf, A.A.; Hussein, S.; Tohamy, A.F.; Marouf, S.; Yassa, H.D.; Zaki, A.R.; Bishayee, A. Protective effect of Echinacea purpurea (Immulant) against cisplatin-induced immunotoxicity in rats. Daru, 2019, 27(1), 233-241.
[http://dx.doi.org/10.1007/s40199-019-00265-4] [PMID: 31134491]
[7]
Castro, E.S.; Bello, M.; Hernández, M.; Correa, J.; Murillo, J.I.; Rosales, M.C.; Muñoz, M. In vitro and in silico evaluation of fucosterol from Sargassum horridum as potential human acetylcholinesterase inhibitor. J. Biomol. Struct. Dyn., 2018, 8, 1-28.
[http://dx.doi.org/10.1080/07391102.2018.1505551]
[8]
Liu, J.; Luthuli, S.; Yang, Y.; Cheng, Y.; Zhang, Y.; Wu, M.; Choi, J.I.; Tong, H. Therapeutic and nutraceutical potentials of a brown seaweed Sargassum fusiforme. Food Sci. Nutr., 2020, 8(10), 5195-5205.
[http://dx.doi.org/10.1002/fsn3.1835] [PMID: 33133523]
[9]
Louime, C.; Fortune, J.; Gervais, G. Sargassum invasion of coastal environments: A growing concern. Am. J. Environ. Sci., 2017, 13(1), 58-64.
[http://dx.doi.org/10.3844/ajessp.2017.58.64]
[10]
van Tussenbroek, B.I.; Hernández Arana, H.A.; Rodríguez-Martínez, R.E.; Espinoza-Avalos, J.; Canizales-Flores, H.M.; González-Godoy, C.E.; Barba-Santos, M.G.; Vega-Zepeda, A.; Collado-Vides, L. Severe impacts of brown tides caused by Sargassum spp. on near-shore Caribbean seagrass communities. Mar. Pollut. Bull., 2017, 122(1-2), 272-281.
[http://dx.doi.org/10.1016/j.marpolbul.2017.06.057] [PMID: 28651862]
[11]
Schell, J.; Goodwin, D.; Siuda, A. Recent Sargassum inundation events in the caribbean: Shipboard observations reveal dominance of a previously rare form. Oceanography (Wash. D.C.), 2015, 28(3), 8-10.
[http://dx.doi.org/10.5670/oceanog.2015.70]
[12]
Heller, R. A Sea Within a Sea: Secrets of the Sargasso, 1sd ed.; Grosset & Dunlap, 2000.
[13]
Susithra, E.; Ramseshu, K.V.; Meena, S.; Veni, V.G. Bench top bioassays -an animal sparing bioassay for anti-tumor compounds. J. Glob. Trends Pharm. Sci., 2011, 2(1), 79-90.
[14]
Van Meerloo, J.; Kaspers, G.J.L.; Cloos, J. Cell sensitivity assays: The MTT assay. In: Cancer Cell Culture; , 2011, pp. 237-245.
[http://dx.doi.org/10.1007/978-1-61779-080-5_20]
[15]
Morris, G.M.; Huey, R.; Lindstrom, W.; Sanner, M.F.; Belew, R.K.; Goodsell, D.S.; Olson, A.J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem., 2009, 30(16), 2785-2791.
[http://dx.doi.org/10.1002/jcc.21256] [PMID: 19399780]
[16]
Frisch, M.J.; Trucks, G.W.; Schlegel, H.B.; Scuseria, G.E.; Robb, M.A.; Cheeseman, J.R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G.A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H.P.; Izmaylov, A.F.; Bloino, J.; Zheng, G.; Sonnenberg, J.L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J.A.; Peralta, J.E.; Ogliaro, F.; Bearpark, M.; Heyd, J.J. Brothers, Kudin, K.N.; Staroverov, V.N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J.C.; Iyengar, S.S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J.M.; Klene, M.; Knox, J.E.; Cross, J.B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R.E.; Yazyev, O.; Austin, A.J.; Cammi, R.; Pomelli, C.; Ochterski, J.W.; Martin, R.L.; Morokuma, K.; Zak rzewski, V.G.; Voth, G.A.; Salvador, P.; Dannenberg, J.J.; Dap prich, S.; Daniels, A.D.; Farkas, Ö.; Foresman, J.B.; Ortiz, J.V.; Cioslowski, J.; Fox, D.J. Gaussian 09, Revision E.01; Gaussian, Inc.: Wallingford, CT, 2009.
[17]
Clarkson, C.; Maharaj, V.J.; Crouch, N.R.; Grace, O.M.; Pillay, P.; Matsabisa, M.G.; Bhagwandin, N.; Smith, P.J.; Folb, P.I. In vitro antiplasmodial activity of medicinal plants native to or naturalised in South Africa. J. Ethnopharmacol., 2004, 92(2-3), 177-191.
[http://dx.doi.org/10.1016/j.jep.2004.02.011] [PMID: 15137999]
[18]
Meyer, B.N.; Ferrigni, N.R.; Putnam, J.E.; Jacobsen, L.B.; Nichols, D.E.; McLaughlin, J.L. Brine shrimp: A convenient general bioassay for active plant constituents. Planta Med., 1982, 45(5), 31-34.
[http://dx.doi.org/10.1055/s-2007-971236] [PMID: 17396775]
[19]
McLaughlin, J.L.; Rogers, L.L.; Anderson, J.E. The use of biological assays to evaluate botanicals. Drug Inf. J., 1998, 32(2), 513-524.
[http://dx.doi.org/10.1177/009286159803200223]
[20]
Ntungwe, N. E.; Domínguez-Martín, E.M.; Roberto, A.; Tavares, J.; Isca, V.M.S.; Pereira, P.; Cebola, M.J.; Rijo, P. Artemia species: An important tool to screen general toxicity samples. Curr. Pharm. Des., 2020, 26(24), 2892-2908.
[http://dx.doi.org/10.2174/1381612826666200406083035] [PMID: 32250221]
[21]
Zandi, K.; Ahmadzadeh, S.; Tajbakhsh, S.; Rastian, Z.; Yousefi, F.; Farshadpour, F.; Sartavi, K. Anticancer activity of Sargassum oligocystum water extract against human cancer cell lines. Eur. Rev. Med. Pharmacol. Sci., 2010, 14(8), 669-673.
[PMID: 20707286]
[22]
Hero, T.; Bühler, H.; Kouam, P.N.; Priesch-Grzeszowiak, B.; Lateit, T.; Adamietz, I.A. The triple-negative breast cancer cell line MDA-MB 231 is specifically inhibited by the ionophore salinomycin. Anticancer Res., 2019, 39(6), 2821-2827.
[http://dx.doi.org/10.21873/anticanres.13410] [PMID: 31177119]
[23]
Wigger, D.; Gulbins, E.; Kleuser, B.; Schumacher, F. Monitoring the sphingolipid de novo synthesis by stable-isotope labeling and liquid chromatography-mass spectrometry. Front. Cell Dev. Biol., 2019, 7, 210.
[http://dx.doi.org/10.3389/fcell.2019.00210] [PMID: 31632963]
[24]
Deng, J.; Gutiérrez, L.G.; Stoll, G.; Motiño, O.; Martins, I.; Núñez, L.; Bravo-San Pedro, J.M.; Humeau, J.; Bordenave, C.; Pan, J.; Fohrer-Ting, H.; Souquere, S.; Pierron, G.; Hetz, C.; Villalobos, C.; Kroemer, G.; Senovilla, L. Paradoxical implication of BAX/BAK in the persistence of tetraploid cells. Cell Death Dis., 2021, 12(11), 1039.
[http://dx.doi.org/10.1038/s41419-021-04321-3]
[25]
Zhang, Q.F.; Li, J.; Bi, F.C.; Liu, Z.; Chang, Z.Y.; Wang, L.Y.; Huang, L.Q.; Yao, N. Ceramide-induced cell death depends on calcium and caspase-like activity in rice. Front Plant Sci, 2020, 11, 145.
[http://dx.doi.org/10.3389/fpls.2020.00145]
[26]
Ferrari, D.; Pinton, P.; Campanella, M.; Callegari, M.G.; Pizzirani, C.; Rimessi, A.; Di Virgilio, F.; Pozzan, T.; Rizzuto, R. Functional and structural alterations in the endoplasmic reticulum and mitochondria during apoptosis triggered by C2-ceramide and CD95/APO-1/FAS receptor stimulation. Biochem. Biophys. Res. Commun., 2010, 391(1), 575-581.
[http://dx.doi.org/10.1016/j.bbrc.2009.11.101] [PMID: 19941832]
[27]
Pitman, M.R.; Pitson, S.M. Inhibitors of the sphingosine kinase pathway as potential therapeutics. Curr. Cancer Drug Targets, 2010, 10(4), 354-367.
[http://dx.doi.org/10.2174/156800910791208599] [PMID: 20370685]
[28]
Vettorazzi, M.; Angelina, E.; Lima, S.; Gonec, T.; Otevrel, J.; Marvanova, P.; Padrtova, T.; Mokry, P.; Bobal, P.; Acosta, L.M.; Palma, A.; Cobo, J.; Bobalova, J.; Csollei, J.; Malik, I.; Alvarez, S.; Spiegel, S.; Jampilek, J.; Enriz, R.D. An integrative study to identify novel scaffolds for sphingosine kinase 1 inhibitors. Eur. J. Med. Chem., 2017, 139, 461-481.
[http://dx.doi.org/10.1016/j.ejmech.2017.08.017] [PMID: 28822281]
[29]
Neubauer, H.A.; Pham, D.H.; Zebol, J.R.; Moretti, P.A.; Peterson, A.L.; Leclercq, T.M.; Chan, H.; Powell, J.A.; Pitman, M.R.; Samuel, M.S.; Bonder, C.S.; Creek, D.J.; Gliddon, B.L.; Pitson, S.M. An oncogenic role for sphingosine kinase 2. Oncotarget, 2016, 7(40), 64886-64899.
[http://dx.doi.org/10.18632/oncotarget.11714]
[30]
Van Brocklyn, J.R.; Lee, M.J.; Menzeleev, R.; Olivera, A.; Edsall, L.; Cuvillier, O.; Thomas, D.M.; Coopman, P.J.; Thangada, S.; Liu, C.H.; Hla, T.; Spiegel, S. Dual actions of sphingosine-1-phosphate: Extracellular through the Gi-coupled receptor Edg-1 and intracellular to regulate proliferation and survival. J. Cell Biol., 1998, 142(1), 229-240.
[http://dx.doi.org/10.1083/jcb.142.1.229]
[31]
Nava, V.E.; Hobson, J.P.; Murthy, S.; Milstien, S.; Spiegel, S. Sphingosine kinase type 1 promotes estrogen-dependent tumorigenesis of breast cancer MCF-7 cells. Exp. Cell Res., 2002, 281(1), 115-127.
[http://dx.doi.org/10.1006/excr.2002.5658] [PMID: 12441135]
[32]
Sarkar, S.; Maceyka, M.; Hait, N.C.; Paugh, S.W.; Sankala, H.; Milstien, S.; Spiegel, S. Sphingosine kinase 1 is required for migration, proliferation and survival of MCF-7 human breast cancer cells. FEBS Lett., 2005, 579(24), 5313-5317.
[http://dx.doi.org/10.1016/j.febslet.2005.08.055] [PMID: 16194537]
[33]
Struckhoff, A.P.; Bittman, R.; Burow, M.E.; Clejan, S.; Elliott, S.; Hammond, T.; Tang, Y.; Beckman, B.S. Novel ceramide analogs as potential chemotherapeutic agents in breast cancer. J. Pharmacol. Exp. Ther., 2004, 309(2), 523-532.
[http://dx.doi.org/10.1124/jpet.103.062760] [PMID: 14742741]
[34]
Mathiasen, I.S.; Hansen, C.M.; Foghsgaard, L.; Jäättelä, M. Sensitization to TNF-induced apoptosis by 1,25-dihydroxy vitamin D(3) involves up-regulation of the TNF receptor 1 and cathepsin B. Int. J. Cancer, 2001, 93(2), 224-231.
[http://dx.doi.org/10.1002/ijc.1325]
[35]
Cuvillier, O.; Edsall, L.; Spiegel, S. Involvement of sphingosine in mitochondria-dependent Fas-induced apoptosis of type II Jurkat T cells. J. Biol. Chem., 2000, 275(21), 15691-15700.
[http://dx.doi.org/10.1074/jbc.M000280200] [PMID: 10747891]
[36]
Ahn, E.H.; Schroeder, J.J. Induction of apoptosis by sphingosine, sphinganine, and C(2)-ceramide in human colon cancer cells, but not by C(2)-dihydroceramide. Anticancer Res., 2010, 30(7), 2881-2884.
[PMID: 20683027]
[37]
Ryland, L.K.; Fox, T.E.; Liu, X.; Loughran, T.P.; Kester, M. Dysregulation of sphingolipid metabolism in cancer. Cancer Biol. Ther., 2011, 11(2), 138-149.
[http://dx.doi.org/10.4161/cbt.11.2.14624] [PMID: 21209555]
[38]
Bu, Y.; Wu, H.; Deng, R.; Wang, Y. Therapeutic potential of SphK1 inhibitors based on abnormal expression of SphK1 in inflammatory immune related-diseases. Front. Pharmacol., 2021, 12, 733387.
[http://dx.doi.org/10.3389/fphar.2021.733387]
[39]
Ahn, E.H.; Chang, C.C.; Schroeder, J.J. Evaluation of sphinganine and sphingosine as human breast cancer chemotherapeutic and chemopreventive agents. Exp. Biol. Med. (Maywood), 2006, 231(10), 1664-1672.
[http://dx.doi.org/10.1177/153537020623101012] [PMID: 17060688]
[40]
Ahn, E.H.; Yang, H.; Hsieh, C.Y.; Sun, W.; Chang, C.C.; Schroeder, J.J. Evaluation of chemotherapeutic and cancer-protective properties of sphingosine and C2-ceramide in a human breast stem cell derived carcinogenesis model. Int. J. Oncol., 2019, 54(2), 655-664.
[http://dx.doi.org/10.3892/ijo.2018.4641] [PMID: 30483770]

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