Skip to main content
Log in

Cytotoxicity screening of supercritical fluid extracted seaweeds and phenylpropanoids

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Detached leaves of Posidonia oceanica and Zostera marina creating nuisance at the shores were extracted by means of supercritical CO2 enriched with a co-solvent, compared with that of soxhlet extraction. The extracts and their active compounds which are phenylpropanoids (chicoric, p-coumaric, rosmarinic, benzoic, ferulic and caffeic acids) were screened for cytotoxicity in cancer cell lines including human breast adenocarcinoma (MCF-7, MDA-MB-231, SK-BR-3), human colon adenocarcinoma (HT-29), human cervix adenocarcinoma (HeLa), human prostate adenocarcinoma (PC-3), Mus musculus neuroblastoma (Neuro 2A) cell lines and African green monkey kidney (VERO) as healthy cell line. Supercritical CO2 extracts proved to be more active than soxhlet counterparts. Particularly, Zostera marina extract obtained by supercritical CO2 at 250 bar, 80 °C, 20% co-solvent and a total flow rate of 15 g/min revealed the best IC50 values of 25, 20, 8 μg/ml in neuroblastoma, colon and cervix cancer cell lines. Among the major compounds tested, p-coumaric acid exhibited the highest cytotoxic against colon and cervix cell lines by with IC50 values of 25, 11 μg/ml. As for the effects on healthy cells, the extract was not cytotoxic indicating a selective cytotoxicity. Obtained supercritical CO2 extracts can be utilized as a supplement for preventive purposes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Explore related subjects

Discover the latest articles and news from researchers in related subjects, suggested using machine learning.

References

  1. Venkata Mohan S, Nikhil GN, Chiranjeevi P, Nagendranatha Reddy C, Rohit MV, Kumar AN, Sarkar O (2016) Waste biorefinery models towards sustainable circular bioeconomy: critical review and future perspectives. Bioresour Technol 215:2–12

    Article  CAS  PubMed  Google Scholar 

  2. Benelli P, Riehl CAS, Smania A, Smania EFA, Ferreira SRS (2010) Bioactive extracts of orange (Citrus sinensis L. Osbeck) pomace obtained by SFE and low pressure techniques: mathematical modeling and extract composition. J Supercrit Fluids 55:132–141

    Article  CAS  Google Scholar 

  3. Yoshida K, Kusaki J, Ehara K, Saka S (2005) Characterization of low molecular weight organic acids from beech wood treated in supercritical water. Appl Biochem Biotechnol 123:795–806

    Article  Google Scholar 

  4. Zhang Q, Zhao M, Xu Q, Ren H, Yin J (2018) Enhanced enzymatic hydrolysis of sorghum stalk by supercritical carbon dioxide and ultrasonic pretreatment. Appl Biochem Biotechnol. https://doi.org/10.1007/s12010-018-2909-x

    Article  PubMed  PubMed Central  Google Scholar 

  5. Kazan A, Koyu H, Turu IC, Yesil-Celiktas O (2014) Supercritical fluid extraction of Prunus persica leaves and utilization possibilities as a source of phenolic compounds. J Supercrit Fluids 92:55–59

    Article  CAS  Google Scholar 

  6. Pilavtepe M, Sargin S, Celiktas MS, Yesil-Celiktas O (2013) Transformation of Posidonia oceanica residues to bioethanol. Ind Crops Prod 51:348–354

    Article  CAS  Google Scholar 

  7. Davies P, Morvan C, Sire O (2007) Structure and properties of fibres from sea-grass (Zostera marina). J Mater Sci 42:4850–4857

    Article  CAS  Google Scholar 

  8. Vergeer HT, Develi A (1997) Phenolic acids in healthy and infected leaves of Zostera marina and their growth-limiting properties towards Labyrinthula zosterae. Aquat Bot 58:65–72

    Article  CAS  Google Scholar 

  9. Chakraborty K, Lipton AP, Paulraj R, Chakraborty RD (2010) Guaiane sesquiterpenes from seaweed Ulva fasciata Delile and their antibacterial properties. Eur J Med Chem 45:2237–2244

    Article  CAS  PubMed  Google Scholar 

  10. Zizic JB, Vukovic NL, Jadranin MB, Andelkovic BD, Tesevic VV, Kacaniova MM, Sukdolak SB, Markovic SD (2013) Chemical composition, cytotoxic and antioxidative activities of ethanolic extracts of propolis on HCT-116 cell line. J Mater Sci 93:3001–3009

    CAS  Google Scholar 

  11. Nepali K, Sharma S, Sharma M, Bedi PMS, Dhar KL (2014) Rational approaches, design strategies, structure activity relationship and mechanistic insights for anticancer hybrids. Eur J Med Chem 77:422–487

    Article  CAS  PubMed  Google Scholar 

  12. PR Newswire (2017) International Seaweed Expo kicks off on Wando Island. https://www.prnewswire.com/news-releases/expo-sheds-light-on-seaweeds-potential-for-future-industries-300440128.html. Accessed 3 Jan 2019

  13. Kumar CS, Sarada DVL, Thomas PG, Rengasamy R (2008) Antibacterial activity of three South Indian seagrasses, Cymodocea serrulata, Halophila ovalis and Zostera capensis. World J Microbiol Biotechnol 24:1989–1992

    Article  Google Scholar 

  14. Rosinha Grundtvig IP, Heintz S, Krühne U, Gernaey KV, Adlercreutz P, Hayler JD, Wells AS, Woodley JM (2018) Screening of organic solvents for bioprocesses using aqueous-organic two-phase systems. Biotechnol Adv 36:1801–1814

    Article  CAS  PubMed  Google Scholar 

  15. Alpak I, AskinUzel R, Sargin S, Yesil-Celiktas O (2018) Supercritical CO2 extraction of an immunosuppressant produced by solid-state fermentation. J CO2 Util 27:398–404

    Article  CAS  Google Scholar 

  16. Grijó DR, Osorio IAV, Cardozo-Filho L (2018) Supercritical extraction strategies using CO2 and ethanol to obtain cannabinoid compounds from Cannabis hybrid flowers. J CO2 Util 28:174–180

    Article  CAS  Google Scholar 

  17. Yesil-Celiktas O, Otto F, Gruener S, Parlar H (2009) Determination of extractability of pine bark using supercritical CO2 extraction and different solvents—optimization and prediction. J Agric Food Chem 57:341–347

    Article  CAS  PubMed  Google Scholar 

  18. Rudyk S, Spirov P, Tyrovolas A (2018) Effect of temperature on crude oil extraction by SC-CO2 at 40–70  °C and 40–60 Mpa. J CO2 Util 24:471–478

    Article  CAS  Google Scholar 

  19. Sang J, Wang H, Jin J, Meng H (2017) Comparison and modelling of rutin solubility in supercritical carbon dioxide and subcritical 1,1,1,2-tetrafluoroethane. J CO2 Util 21:1–8

    Article  CAS  Google Scholar 

  20. Pilavtepe M, Yesil-Celiktas O (2013) Mathematical modeling and mass transfer considerations in supercritical fluid extraction of Posidonia oceanica residues. J Supercrit Fluids 82:244–250

    Article  CAS  Google Scholar 

  21. Pilavtepe M, Yucel M, Helvaci SS, Demircioglu M, Yesil-Celiktas O (2012) Optimization and mathematical modeling of mass transfer between Zostera marina residues and supercritical CO2 modified with ethanol. J Supercrit Fluids 68:87–93

    Article  CAS  Google Scholar 

  22. Akay S, Alpak I, Yesil-Celiktas O (2011) Effects of process parameters on supercritical CO2 extraction of total phenols from strawberry (Arbutus unedo L.) fruits: an optimization study. J Sep Sci 34:1925–1931

    Article  CAS  PubMed  Google Scholar 

  23. Sevimli-Gur C, Cetin B, Akay S, Gulce-Iz S, Yesil-Celiktas O (2013) Extracts from black carrot tissue culture as potent anticancer agents. Plant Foods Hum Nutr 68:293–298

    Article  PubMed  Google Scholar 

  24. Pilavtepe M, Sargin S, Celiktas MS, Yesil-Celiktas O (2012) An integrated process for conversion of Zostera marina residues to bioethanol. J Supercrit Fluids 68:117–122

    Article  CAS  Google Scholar 

  25. Yildiz-Ozturk E, Tag O, Yesil-Celiktas O (2014) Subcritical water extraction of steviol glycosides from Stevia rebaudiana leaves and characterization of the raffinate phase. J Supercrit Fluids 95:422–430

    Article  CAS  Google Scholar 

  26. Shamsabadi FT, Khoddami A, Fard SG, Abdullah R, Othman HH, Mohamed S (2013) Comparison of tamoxifen with edible seaweed (Eucheuma cottonii L.) extract in suppressing breast tumor. Nutr Cancer 65:255–262

    Article  PubMed  Google Scholar 

  27. Kumar SC, Gadewal N, Mohammed SMM (2013) Identification of leads from marine seaweeds against human beta-tubulin. Lett Drug Des Discov 10:67–74

    Article  Google Scholar 

  28. Kong CS, Jeong CH, Choi JS, Kim KJ, Jeong JW (2013) Antiangiogenic effects of p-coumaric acid in human endothelial cells. Phytotheraphy Research 27:317–323

    Article  CAS  Google Scholar 

  29. Xavier CPR, Lima CF, Fernandes-Ferreira M (2009) Salvia fruticosa, Salvia officinalis, and rosmarinic acid induce apoptosis and inhibit proliferation of human colorectal cell lines: the role in MAPK/ERK pathway. Nutr Cancer 61:564–571

    Article  CAS  PubMed  Google Scholar 

  30. Sharmila R, Manoharan S (2012) Anti-tumor activity of rosmarinic acid in 7,12–dimethylbenz(a)anthracene (DMBA) induced skin carcinogenesis in Swiss albino mice. Indian J Exp Biol 50:187–194

    CAS  PubMed  Google Scholar 

  31. Huntimer ED, Halaweish FT, Chase CCL (2006) Proliferative activity of Echinacea angustifolia root extracts on cancer cells: interference with doxorubicin cytotoxicity. Chem Biodivers 3:695–703

    Article  CAS  PubMed  Google Scholar 

  32. Akgun H, Berk B, Erol DD, Mercanoglu G, Bayrak OF, Caglayan B, Dedeagac A, Kurnaz IA (2009) Nitric oxide releasing derivatives of [(2-chloroethyl)ureido] benzoic acid esters as potential antineoplastic agent. Turk J Chem 33:107–121

    CAS  Google Scholar 

  33. Huang MT, Ma W, Yen P, Xie JG, Han JK, Frenkel K, Grunberger D, Conney AH (1996) Inhibitory effects of caffeic acid phenethyl ester (CAPE) on 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion in mouse skin and the synthesis of DNA, RNA and protein in HeLa cells. Carcinogenesis 17:761–765

    Article  CAS  PubMed  Google Scholar 

  34. Hemaiswarya S, Doble M (2013) Combination of phenylpropanoids with 5-fluorouracil as anticancer agents against human cervical cancer (HeLa) cell line. Phytomedicine 20:151–158

    Article  CAS  PubMed  Google Scholar 

  35. Kuenzig W, Chau J, Norkus E, Holowaschenko H, Newmark H, Mergens W, Conney AH (1984) Caffeic and ferulic acid as blockers of nitrosamine formation. Carcinogenesis 5:309–313

    Article  CAS  PubMed  Google Scholar 

  36. Barbaric M, Miskovic K, Bojic M, Loncar MB, Smolcic-Bubalo A, Debeljak Z, Medic-Saric M (2011) Chemical composition of the ethanolic propolis extracts and its effect on HeLa cells. J Ethnopharmacol 135:772–778

    Article  CAS  PubMed  Google Scholar 

  37. Zhang S, Huang Y, Li Y, Wang Y, He X (2019) Anti-neuroinflammatory and antioxidant phenylpropanoids from Chinese olive. Food Chem 286:421–427

    Article  CAS  PubMed  Google Scholar 

  38. Yoon SA, Kang SI, Shin HS (2013) p-Coumaric acid modulates glucose and lipid metabolism via AMP-activated protein kinase in L6 skeletal muscle cells. Biochem Biophys Res Commun 432:553–557

    Article  CAS  PubMed  Google Scholar 

  39. Jung CH, Jun CY, Lee S, Park CH, Cho K, Ko SG (2006) Rhus verniciflua stokes extract: radical scavenging activities and protective effects on H2O2-induced cytotoxicity in macrophage RAW 264.7 cell lines. Biol Pharm Bull 29:1603–1607

    Article  CAS  PubMed  Google Scholar 

  40. Gokce G, Haznedaroglu MZ (2008) Evaluation of antidiabetic, antioxidant and vasoprotective effects of Posidonia oceanica extract. J Ethnopharmacol 115:122–130

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The financial support provided by the Research Fund of Kocaeli University (KOU-BAP 2013/022) and Türkiye Bilimsel ve Teknolojik Araştirma Kurumu (110M790) are appreciated. Additionally, authors are thankful to Dr. Halim Aytekin Ergul for providing the seaweed samples.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ozlem Yesil-Celiktas.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sevimli-Gur, C., Yesil-Celiktas, O. Cytotoxicity screening of supercritical fluid extracted seaweeds and phenylpropanoids. Mol Biol Rep 46, 3691–3699 (2019). https://doi.org/10.1007/s11033-019-04812-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-019-04812-9

Keywords

Profiles

  1. Ozlem Yesil-Celiktas