title: Can macroalgae provide promising anti-tumoral compounds? A closer look at Cystoseira tamariscifolia as a source for antioxidant and anti-hepatocarcinoma compounds.
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 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (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 bromodeoxyuridine (BrdU) incorporation assay. CTH-treated HepG2 cells presented also pro-apoptotic features, such as increased Annexin V/propidium iodide (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.
authors.affiliation: Centre of Marine Sciences, Faculty of Sciences and Technology, Campus of Gambelas, University of Algarve , Faro , Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Vizetto-Duarte
authors.affiliation: Centre of Marine Sciences, Faculty of Sciences and Technology, Campus of Gambelas, University of Algarve , Faro , Portugal.
authors.forename: Luísa
authors.initials: L
authors.lastname: Custódio
authors.affiliation: Institute for Research in Biomedicine of Barcelona, Chemistry and Molecular Pharmacology, Barcelona Science Park, Baldiri Reixac, Barcelona, Spain; CIBER-BNN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, Baldiri Reixac, Barcelona, Spain.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Acosta
authors.affiliation: Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of Sao Paulo , São Paulo , Brazil.
authors.forename: João H G
authors.initials: JH
authors.lastname: Lago
authors.affiliation: Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of Sao Paulo , São Paulo , Brazil.
authors.forename: Thiago R
authors.initials: TR
authors.lastname: Morais
authors.affiliation: Centre of Marine Sciences, Faculty of Sciences and Technology, Campus of Gambelas, University of Algarve , Faro , Portugal.
authors.forename: Carolina
authors.initials: C
authors.lastname: Bruno de Sousa
authors.affiliation: Centre of Marine Sciences, Faculty of Sciences and Technology, Campus of Gambelas, University of Algarve, Faro, Portugal; Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Lisbon, Portugal.
authors.forename: Katkam N
authors.initials: KN
authors.lastname: Gangadhar
authors.affiliation: Centre of Marine Sciences, Faculty of Sciences and Technology, Campus of Gambelas, University of Algarve , Faro , Portugal.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Rodrigues
authors.affiliation: Centre of Marine Sciences, Faculty of Sciences and Technology, Campus of Gambelas, University of Algarve , Faro , Portugal.
authors.forename: Hugo
authors.initials: H
authors.lastname: Pereira
authors.affiliation: i3S-Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Rua Alfredo Allen, Porto, Portugal; IPATIMUP-Institute of Molecular Pathology and Immunology of the University of Porto, Cancer Drug Resistance Group, Rua Júlio Amaral de Carvalho, Porto, Portugal; Faculty of Medicine of the University of Porto, Department of Pathology and Oncology, Alameda Prof. Hernâni Monteiro, Porto, Portugal.
authors.forename: Raquel T
authors.initials: RT
authors.lastname: Lima
authors.affiliation: i3S-Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Rua Alfredo Allen, Porto, Portugal; IPATIMUP-Institute of Molecular Pathology and Immunology of the University of Porto, Cancer Drug Resistance Group, Rua Júlio Amaral de Carvalho, Porto, Portugal; Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo FerreiraPorto, Portugal.
authors.forename: M Helena
authors.initials: MH
authors.lastname: Vasconcelos
authors.affiliation: Centre of Marine Sciences, Faculty of Sciences and Technology, Campus of Gambelas, University of Algarve , Faro , Portugal.
authors.forename: Luísa
authors.initials: L
authors.lastname: Barreira
authors.affiliation: Center of Chemistry and Biochemistry, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Lisbon , Lisbon , Portugal.
authors.forename: Amélia P
authors.initials: AP
authors.lastname: Rauter
authors.affiliation: Institute for Research in Biomedicine of Barcelona, Chemistry and Molecular Pharmacology, Barcelona Science Park, Baldiri Reixac, Barcelona, Spain; CIBER-BNN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, Baldiri Reixac, Barcelona, Spain; Department of Organic Chemistry, University of Barcelona, Martí i Franqués, Barcelona, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
authors.affiliation: Centre of Marine Sciences, Faculty of Sciences and Technology, Campus of Gambelas, University of Algarve , Faro , Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Varela
keywords: Anti-hepatocarcinoma; Antioxidant; Brown algae; Cystoseira; Marine natural products