Can macroalgae provide promising anti-tumoral compounds? A closer look at Cystoseira tamariscifolia as a source for antioxidant and anti-hepatocarcinoma compounds

Catarina Vizetto-Duarte; Luísa Custódio; Gerardo Acosta; João H G Lago; Thiago R Morais; Carolina Bruno de Sousa; Katkam N Gangadhar; Maria João Rodrigues; Hugo Pereira; Raquel T Lima; M. Helena Vasconcelos; Luísa Barreira; Amélia P Rauter; Fernando Albericio; João Varela

doi:10.7287/peerj.preprints.1527v1

Can macroalgae provide promising anti-tumoral compounds? A closer look at Cystoseira tamariscifolia as a source for antioxidant and anti-hepatocarcinoma compounds

Catarina Vizetto-Duarte¹, Luísa Custódio¹, Gerardo Acosta^2,3,4, João H G Lago⁵, Thiago R Morais⁵, Carolina Bruno de Sousa¹, Katkam N Gangadhar^1,6, Maria João Rodrigues¹, Hugo Pereira¹, Raquel T Lima^7,8,9, M. Helena Vasconcelos^8,10,11, Luísa Barreira¹, Amélia P Rauter¹², Fernando Albericio^2,3,13, João Varela ¹

1 University of Algarve, Campus de Gambelas, Centre of Marine Sciences, Faro, Portugal

2 Barcelona Science Park, Institute for Research in Biomedicine, Barcelona, Spain

3 Barcelona Science Park, CIBER-BNN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona, Spain

4 Chemistry and Molecular Pharmacology, Institute for Research Biomedicine of Barcelona, Barcelona, Spain

5 Federal University of Sao Paulo, Institute of Environmental, Chemical and Pharmaceutical Sciences, São Paulo, Brazil

6 Universidade Nova de Lisboa, Instituto de Tecnologia Química e Biológica, Lisbon, Portugal

7 i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal

8 Cancer Drug Resistance Group, IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal

9 Department of Pathology and Oncology, Faculty of Medicine, University of Porto, Porto, Portugal

10 Cancer Drug Resistance Group, i3S - Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Porto, Portugal

11 Department of Biological Sciences, Faculty of Pharmacy of the University of Porto, Porto, Portugal

12 Department of Chemistry and Biochemistry, Faculty of Sciences University of Lisbon, Center of Chemistry and Biochemistry, Lisbon, Portugal

13 Department of Organic Chemistry, University of Barcelona, Barcelona, Spain

DOI: 10.7287/peerj.preprints.1527v1

Published: 2015-11-24
Accepted: 2015-11-24

Subject Areas: Biotechnology, Marine Biology
Keywords: Marine natural products, brown algae, antioxidant, anti-hepatocarcinoma, Cystoseira

Licence: This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ PrePrints) and either DOI or URL of the article must be cited.

Cite this article: Vizetto-Duarte C, Custódio L, Acosta G, Lago JHG, Morais TR, Bruno de Sousa C, Gangadhar KN, Rodrigues MJ, Pereira H, Lima RT, Vasconcelos MH, Barreira L, Rauter AP, Albericio F, Varela J. 2015. Can macroalgae provide promising anti-tumoral compounds? A closer look at Cystoseira tamariscifolia as a source for antioxidant and anti-hepatocarcinoma compounds. PeerJ PrePrints 3:e1527v1 https://doi.org/10.7287/peerj.preprints.1527v1

Abstract

Marine organisms are a prolific source of drug leads in a variety of therapeutic areas. In the last few years, biomedical, pharmaceutical and nutraceutical industries have shown growing interest in novel compounds from marine organisms, including macroalgae. Cystoseira is a genus of Phaeophyceae (Fucales) macroalgae known to contain bioactive compounds. Organic extracts (hexane, diethyl ether, ethyl acetate and methanol extracts) from three Cystoseira species (C. humilis, C. tamariscifolia and C. usneoides) were evaluated for their total phenolic content, radical scavenging activity against DPPH and ABTS radicals, and antiproliferative activity against a human hepatocarcinoma cell line (HepG2 cells). C. tamariscifolia had the highest TPC and RSA. The hexane extract of C. tamariscifolia (CTH) had the highest cytotoxic activity (IC50=2.31 µg/mL), and was further tested in four human tumor (cervical adenocarcinoma HeLa; gastric adenocarcinoma AGS; colorectal adenocarcinoma HCT-15; neuroblastoma SH-SY5Y), and two non-tumor (murine bone marrow stroma S17 and human umbilical vein endothelial HUVEC) cell lines in order to determine its selectivity. CTH strongly reduced viability of all tumor cell lines, especially of HepG2 cells. Cytotoxicity was particularly selective for the latter cells with a selectivity index = 12.6 as compared to non-tumor cells. Incubation with CTH led to a 2-fold decrease of HepG2 cell proliferation as shown by the BrdU incorporation assay. CTH-treated HepG2 cells presented also pro-apoptotic features, such as increased Annexin V/PI binding and dose-dependent morphological alterations in DAPI-stained cells. Moreover, it had a noticeable disaggregating effect on 3D multicellular tumor spheroids. Demethoxy cystoketal chromane, a derivative of the meroditerpenoid cystoketal, was identified as the active compound in CTH and was shown to display selective in vitro cytotoxicity towards HepG2 cells.

Author Comment

This is a submission to PeerJ for review.