Seasonal variation in the metabolome expression of Jania rubens (Rhodophyta) reveals eicosapentaenoic acid as a potential anticancer metabolite.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
20 09 2023
20 09 2023
Historique:
received:
17
05
2023
accepted:
11
09
2023
medline:
22
9
2023
pubmed:
21
9
2023
entrez:
21
9
2023
Statut:
epublish
Résumé
Seaweeds of the intertidal zone are subjected to diverse stresses due to environmental changes in radiation, salinity, water quality, herbivore communities, etc. Thus, marine seaweeds developed various unique compounds to deal with environmental fluctuations. Therefore, they are a good source of unique novel compounds. Here, we explored the seasonal metabolomic changes in Jania rubens and found notable changes between extracts of different seasons in the metabolomic profile and in their anticancer activity. The most bioactive extract was from samples collected during the Fall season, which demonstrated an LC50 of 178.39 (± 10.02 SD) µg/ml toward Non Small Cell Lung Cancer (NSCLC) followed by the Winter season extract. The Fall and Winter extracts also displayed more resemblance in their metabolic profile relative to Spring and Summer extracts. The Fall extract was fractionated and tested for cytotoxic activity toward an array of cancer cell lines. Eventually, using a bio-guided assay and multiple fractionation steps, we isolated and identified the essential fatty acid, eicosapentaenoic acid, as the active anticancer agent, showing an LC50 of 5.23 (± 0.07 SD) µg/ml toward NSCLC. Our results emphasize the potential use of J. rubens as a source of beneficial fatty acids and stress the importance of environmental effects on metabolic constitutes.
Identifiants
pubmed: 37730882
doi: 10.1038/s41598-023-42497-0
pii: 10.1038/s41598-023-42497-0
pmc: PMC10511708
doi:
Substances chimiques
Eicosapentaenoic Acid
AAN7QOV9EA
Plant Extracts
0
Banques de données
figshare
['10.6084/m9.figshare.22793627']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
15559Informations de copyright
© 2023. Springer Nature Limited.
Références
Saraswati, Giriwono, P. E., Iskandriati, D., Tan, C. P. & Andarwulan, N. Sargassum seaweed as a source of anti-inflammatory substances and the potential insight of the tropical species: A review. Mar. Drugs 17, 1–35 (2019).
doi: 10.3390/md17100590
Sellimi, S. et al. Antioxidant, antibacterial and in vivo wound healing properties of laminaran purified from Cystoseira barbata seaweed. Int. J. Biol. Macromol. 119, 633–644 (2018).
pubmed: 30063934
doi: 10.1016/j.ijbiomac.2018.07.171
Rocha, D. H. A., Seca, A. M. L. & Pinto, D. C. G. A. Seaweed secondary metabolites in vitro and in vivo anticancer activity. Mar. Drugs 16, 1–27 (2018).
doi: 10.3390/md16110410
Pradhan, B. et al. Beneficial effects of seaweeds and seaweed-derived bioactive compounds: Current evidence and future prospective. Biocatal. Agric. Biotechnol. 39, 102242 (2022).
doi: 10.1016/j.bcab.2021.102242
Lomartire, S. & Gonçalves, A. M. M. An overview of potential seaweed-derived bioactive compounds for pharmaceutical applications. Mar. Drugs 20, 1–32 (2022).
doi: 10.3390/md20020141
Cho, M. L. et al. Glioblastoma-specific anticancer activity of pheophorbide a from the edible red seaweed Grateloupia elliptica. J. Microbiol. Biotechnol. 24, 346–353 (2014).
pubmed: 24296458
doi: 10.4014/jmb.1308.08090
Ming, J. X. et al. Fucoxanthin extracted from Laminaria Japonica inhibits metastasis and enhances the sensitivity of lung cancer to Gefitinib. J. Ethnopharmacol. 265, 113302 (2021).
pubmed: 32860893
doi: 10.1016/j.jep.2020.113302
Wijesinghe, W. A. J. P. & Jeon, Y.-J. Biological activities and potential industrial applications of fucose rich sulfated polysaccharides and fucoidans isolated from brown seaweeds: A review. Carbohydr. Polym. 88, 13–20 (2012).
doi: 10.1016/j.carbpol.2011.12.029
Gupta, S. & Abu-Ghannam, N. Bioactive potential and possible health effects of edible brown seaweeds. Trends Food Sci. Technol. 22, 315–326 (2011).
doi: 10.1016/j.tifs.2011.03.011
Lee, H., Selvaraj, B. & Lee, J. W. Anticancer effects of seaweed-derived bioactive compounds. Appl. Sci. 11, 11261 (2021).
doi: 10.3390/app112311261
Wahl, M. et al. Season affects strength and direction of the interactive impacts of ocean warming and biotic stress in a coastal seaweed ecosystem. Limnol. Oceanogr. 65, 807–827 (2020).
doi: 10.1002/lno.11350
Lalegerie, F., Gager, L., Stiger-Pouvreau, V. & Connan, S. The stressful life of red and brown seaweeds on the temperate intertidal zone: Effect of abiotic and biotic parameters on the physiology of macroalgae and content variability of particular metabolites. Adv. Bot. Res. 95, 247–287 (2020).
doi: 10.1016/bs.abr.2019.11.007
Biancacci, C. et al. LC-MSn profiling reveals seasonal variation in the composition of Osmundea pinnatifida (Hudson) Stackhouse. J. Appl. Phycol. 33, 2443–2458 (2021).
doi: 10.1007/s10811-021-02482-4
Gaubert, J., Payri, C. E., Vieira, C., Solanki, H. & Thomas, O. P. High metabolic variation for seaweeds in response to environmental changes: A case study of the brown algae Lobophora in coral reefs. Sci. Rep. 9, 1–12 (2019).
doi: 10.1038/s41598-018-38177-z
Polat, S. & Ozogul, Y. Seasonal proximate and fatty acid variations of some seaweeds from the northeastern Mediterranean coast. Oceanologia 55, 375–391 (2013).
doi: 10.5697/oc.55-2.375
Mansur, A. A., Brown, M. T. & Billington, R. A. The cytotoxic activity of extracts of the brown alga Cystoseira tamariscifolia (Hudson) Papenfuss, against cancer cell lines changes seasonally. J. Appl. Phycol. 32, 2419–2429 (2020).
doi: 10.1007/s10811-019-02016-z
Heavisides, E. et al. Seasonal variations in the metabolome and bioactivity profile of fucus vesiculosus extracted by an optimised, pressurised liquid extraction protocol. Mar. Drugs 16, 1–28 (2018).
doi: 10.3390/md16120503
Einav, R. Seaweeds of the East Mediterranean coast (Bar-Ilan University Press, 2004).
Ktari, L., Blond, A. & Guyot, M. 16β-hydroxy-5α-cholestane-3,6-dione, a novel cytotoxic oxysterol from the red alga Jania rubens. Bioorg. Med. Chem. Lett. 10, 2563–2565 (2000).
pubmed: 11086730
doi: 10.1016/S0960-894X(00)00504-7
Awad, N. E. Bioactive brominated diterpenes from the marine red alga Jania rubens (L.) Lamx. Phyther. Res. 18, 275–279 (2004).
doi: 10.1002/ptr.1273
Ahmed, H. H., Hegazi, M. M., Abd-Alla, H. I., Eskander, E. F. & Ellithey, M. S. Antitumour and antioxidant activity of some red sea seaweeds in Ehrlich ascites carcinoma in vivo. Zeitschrift fur Naturforsch Sect. C J. Biosci. 66, 367–376 (2011).
doi: 10.1515/znc-2011-7-808
Gheda, S., El-Sheekh, M. & Abou-Zeid, A. In vitro anticancer activity of polysaccharide extracted from red alga Jania rubens against breast and colon cancer cell lines. Asian Pac. J. Trop. Med. 11, 583–589 (2018).
doi: 10.4103/1995-7645.244523
El-sheekh, M. M. Antitumor immunity and therapeutic properties of marine seaweeds-derived extracts in the treatment of cancer. Res. Sq. 22, 1–32 (2022).
Awad, N. E. Bioactive brominated diterpenes from the marine red alga Jania rubens (L.) Lamx. Phyther. Res. 18, 275–279 (2004).
doi: 10.1002/ptr.1273
Baram, L. et al. The heterogeneity and complexity of Cannabis extracts as antitumor agents. Oncotarget 10, 4091–4106 (2019).
pubmed: 31289609
pmcid: 6609248
doi: 10.18632/oncotarget.26983
Berman, P. et al. A new ESI-LC/MS approach for comprehensive metabolic profiling of phytocannabinoids in Cannabis. Sci. Rep. https://doi.org/10.1038/s41598-018-32651-4 (2018).
doi: 10.1038/s41598-018-32651-4
pubmed: 30250104
pmcid: 6155167
Wang, M. et al. Sharing and community curation of mass spectrometry data with global natural products social molecular networking. Nat. Biotechnol. 34, 828–837 (2016).
pubmed: 27504778
pmcid: 5321674
doi: 10.1038/nbt.3597
Nothias, L. F. et al. Bioactivity-based molecular networking for the discovery of drug leads in natural product bioassay-guided fractionation. J. Nat. Prod. 81, 758–767 (2018).
pubmed: 29498278
doi: 10.1021/acs.jnatprod.7b00737
Goslee, S. C. & Urban, D. L. The ecodist package for dissimilarity-based analysis of ecological data. J. Stat. Softw. 22, 1–19 (2007).
doi: 10.18637/jss.v022.i07
Oksanen, R J. et al. Title community ecology package. Vegan: Community Ecol. Package (2022).
Hanahan, D., Weinberg, R. A. & Francisco, S. The hallmarks of cancer. Cell 100, 57–70 (2000).
pubmed: 10647931
doi: 10.1016/S0092-8674(00)81683-9
Marshak, A. R. et al. Spatiotemporal dynamics of mediterranean shallow coastal fish communities along a gradient of marine protection. Water 12, 1537 (2020).
doi: 10.3390/w12061537
Influencing, F. & Microalgae, E. Examining the dynamic nature of epiphytic microalgae in the Florida keys: What factors influence community composition. J. Exp. Mar. Bio. Ecol. 538, 151538 (2021).
doi: 10.1016/j.jembe.2021.151538
Gladyshev, M. I., Sushchik, N. N. & Makhutova, O. N. Production of EPA and DHA in aquatic ecosystems and their transfer to the land. Prostaglandins Other Lipid Mediat. https://doi.org/10.1016/j.prostaglandins.2013.03.002 (2013).
doi: 10.1016/j.prostaglandins.2013.03.002
pubmed: 23500063
Sayanova, O. V. & Napier, J. A. Eicosapentaenoic acid: Biosynthetic routes and the potential for synthesis in transgenic plants. Phytochemistry 65, 147–158 (2004).
pubmed: 14732274
doi: 10.1016/j.phytochem.2003.10.017
Robertson, R. et al. Algae-derived polyunsaturated fatty acids: Implications for human health. In Polyunsaturated Fatty Acids: Sources, Antioxidant Properties and Health Benefits (ed. Catalá, A.) 45–99 (Nova Sciences Publishers, Inc, 2013).
Kravchuk, E. S., Ivanova, Æ. E. A., Ageev, A. V. & Kalachova, Æ. G. S. Seasonal dynamics of long-chain polyunsaturated fatty acids in littoral benthos in the upper Yenisei river. Aquat. Ecol. 41, 349–365. https://doi.org/10.1007/s10452-006-9065-z (2007).
doi: 10.1007/s10452-006-9065-z
Ozogul, Y. & Polat, A. Seasonal fat and fatty acids variations of seven marine fish species from the Mediterranean Sea. Eur. J. Lipid Sci. Technol. 113, 1491–1498 (2011).
doi: 10.1002/ejlt.201000554
Sushchik, N. N., Gladyshev, M. I., Kalachova, G. S., Makhutova, O. N. & Ageev, A. V. Comparison of seasonal dynamics of the essential PUFA contents in benthic invertebrates and grayling Thymallus arcticus in the Yenisei river. Comp. Biochem. Physiol. 145, 278–287 (2006).
doi: 10.1016/j.cbpb.2006.05.014
Jiang, H. & Gao, K. Note effects of lowering temperature during culture on the production of polyunsaturated fatty acids in the marine diatom phaeodactylum. J. Appl. Phycol. 654, 651–654 (2004).
doi: 10.1111/j.1529-8817.2004.03112.x
Aussant, J., Guihéneuf, F. & Stengel, D. B. Impact of temperature on fatty acid composition and nutritional value in eight species of microalgae. Appl. Microbiol. Biotechnol. 102, 5279–5297 (2018).
pubmed: 29696337
doi: 10.1007/s00253-018-9001-x
Schmid, M., Guihéneuf, F. & Stengel, D. B. Fatty acid contents and profiles of 16 macroalgae collected from the Irish Coast at two seasons. J. Appl. Phycol. 26, 451–463 (2014).
doi: 10.1007/s10811-013-0132-2
Pereira, H. et al. Polyunsaturated fatty acids of marine macroalgae: Potential for nutritional and pharmaceutical applications. Mar. Drugs 10, 1920–1935 (2012).
pubmed: 23118712
pmcid: 3475264
doi: 10.3390/md10091920
Caf, F., Özdemir, N. Ş, Yılmaz, Ö., Durucan, F. & Ak, İ. Fatty acid and lipophilic vitamin composition of seaweeds from Antalya and Çanakkale (Turkey). Grasas y Aceites 70, 312 (2019).
doi: 10.3989/gya.0704182
Polat, S. & Ozogul, Y. Fatty acid, mineral and proximate composition of some seaweeds from the northeastern mediterranean coast. Ital. J. Food Sci. 21, 317–324 (2009).
Matching, T. & Test, R. Eicosanoids. Hormones (Fourth Ed) 1937, 162–173 (2001).
Tapiero, H., Ba, G. N., Couvreur, P. & Tew, K. D. Polyunsaturated fatty acids (PUFA) and eicosanoids in human health and pathologies. Biomed. Pharmacother. 56, 215–222 (2002).
pubmed: 12199620
doi: 10.1016/S0753-3322(02)00193-2
Narayan, B., Miyashita, K. & Hosakawa, M. Physiological effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—A review physiological effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—A review. Food Rev. Int. ISSN 9129, 291–307 (2006).
doi: 10.1080/87559120600694622
Yao, Q. H. et al. ω-3 polyunsaturated fatty acids inhibit the proliferation of the lung adenocarcinoma cell line A549 in vitro. Mol. Med. Rep. 9, 401–406 (2014).
pubmed: 24276408
doi: 10.3892/mmr.2013.1829
Zajdel, A., Wilczok, A. & Tarkowski, M. Toxic effects of n-3 polyunsaturated fatty acids in human lung A549 cells. Toxicol. In Vitro 30, 486–491 (2015).
pubmed: 26381084
doi: 10.1016/j.tiv.2015.09.013
Wang, W. et al. ω-3 Polyunsaturated fatty acids-derived lipid metabolites on angiogenesis, inflammation and cancer. Prostaglandins Other Lipid Mediat. 113–115, 13–20 (2014).
pubmed: 25019221
doi: 10.1016/j.prostaglandins.2014.07.002
Yang, P. et al. Formation and antiproliferative effect of prostaglandin E3 from eicosapentaenoic acid in human lung cancer cells. J. Lipid Res. 45, 1030–1039 (2004).
pubmed: 14993240
doi: 10.1194/jlr.M300455-JLR200
Yao, Q. et al. Role of autophagy in the ω - 3 long chain polyunsaturated fatty acid-induced death of lung cancer A549 cells. Oncol. Lett. 9, 2736–2742 (2015).
pubmed: 26137138
pmcid: 4473716
doi: 10.3892/ol.2015.3110
Nunes, N., Rosa, G. P., Ferraz, S., Barreto, M. C. & de Carvalho, M. A. A. P. Fatty acid composition, TLC screening, ATR-FTIR analysis, anti-cholinesterase activity, and in vitro cytotoxicity to A549 tumor cell line of extracts of 3 macroalgae collected in Madeira. J. Appl. Phycol. 32, 759–771 (2020).
doi: 10.1007/s10811-019-01884-9
Patterson, E., Wall, R., Fitzgerald, G. F., Ross, R. P. & Stanton, C. Health implications of high dietary omega-6 polyunsaturated fatty acids. J. Nutr. Metab. 2012, 1–16 (2012).
doi: 10.1155/2012/539426
Wang, J. et al. Inhibition of polyunsaturated fatty acids synthesis decreases growth rate and membrane fluidity of Rhodosporidium kratochvilovae at low temperature. Lipids 52, 729–735 (2017).
pubmed: 28660529
doi: 10.1007/s11745-017-4273-y
Cao, M. et al. Integrating transcriptomics and metabolomics to characterize the regulation of EPA biosynthesis in response to cold stress in seaweed Bangia fuscopurpurea. PLoS One 12, 1–16 (2017).
doi: 10.1371/journal.pone.0186986