Planta Med 2014; 80 - SL12
DOI: 10.1055/s-0034-1394500

Antitumoural activity of Cystoseira species: Insights into the mechanism of action

C Vizetto-Duarte 1, MJ Rodrigues 1, H Pereira 1, N Neng 2, JM Florêncio Nogueira 2, H Vasconcelos 3, G Acosta 4, L Custódio 1, L Barreira 1, AP Rauter 2, F Albericio 4, 5, 6, J Varela 1
  • 1Centre of Marine Sciences, University of Algarve, Faculty of Sciences and Technology, Ed. 7, Campus of Gambelas, Faro, Portugal
  • 2Center of Chemistry and Biochemistry, Department of Chemistry and Biochemistry, Faculty of Sciences University of Lisbon, Campo Grande, Ed. C8, Piso 5, 1749 – 016 Lisbon, Portugal
  • 3Cancer Drug Resistance Group, IPATIMUP – Institute of Molecular Pathology and Immunology of the University of Porto, Portugal
  • 4Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028, Barcelona, Spain
  • 5CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028 Barcelona, Spain
  • 6University of Barcelona, Department of Organic Chemistry, Martí i Franqués 1 – 11, 08028 Barcelona, Spain

Brown algae are a rich source of secondary metabolites displaying a wide variety of bioactivities. In this work, four organic extracts (hexane, diethyl ether, ethyl acetate and methanol) from three Cystoseira species (C. humilis, C. tamariscifolia and C. usneoides) were screened for their total phenolic content (TPC), radical scavenging activity (RSA) against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radicals, and in vitro cytotoxic activity against human hepatocarcinoma HepG2 cells. C. tamariscifolia hexane extract (CTH) displayed the highest TPC and RSA, and the most effective cytotoxic activity (IC50= 2.31 µg/mL), and was further evaluated in four human tumoural cell lines, namely HeLa, AGS, HCT-15 and SH-SY5Y cells, as well as two non-tumoural cell lines: murine stromal S17 and human umbilical vein endothelial HUVEC cells. CTH strongly and selectively reduced the viability of all cell lines, especially when compared with HUVEC cells. The decrease in cell viability was associated with apoptosis in HepG2 cells. CTH was submitted to a bio-guided fractionation until the isolation of the major compounds of the bioactive fraction was achieved. This led to the isolation of two compounds, which exhibited in vitro cytotoxic activity against HepG2 cells. Moreover, cytotoxicity was shown to be due to apoptosis through annexin V-FITC staining. In addition, the two compounds completely disrupted the normal cell cycle and altered the expression of apoptosis-related proteins such as p53, PARP, Bcl-2 and procaspase-3. These results suggest that Cystoseira species can be a promising source of interesting compounds with potential biomedical applications.

Acknowledgements: This work was supported by SEABIOMED (PTDC/MAR/103957/2008) and the XtremeBio projects (PTDC/MAR-EST/4346/2012) funded by Foundation for Science and Technology (FCT) and the Portuguese National Budget. CVD is an FCT doctoral research fellow (SFRH/BD/81425/2011).