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
Affiliations
Catarina Vizetto-Duarte
Centre of Marine Sciences, Faculty of Sciences and Technology, Campus of Gambelas, University of Algarve, Faro, Portugal
Luísa Custódio
Centre of Marine Sciences, Faculty of Sciences and Technology, Campus of Gambelas, University of Algarve, Faro, Portugal
Gerardo Acosta
Institute for Research in Biomedicine of Barcelona, Chemistry and Molecular Pharmacology, Barcelona Science Park, Baldiri Reixac, Barcelona, Spain
João H.G. Lago
Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of Sao Paulo, São Paulo, Brazil
Thiago R. Morais
Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of Sao Paulo, São Paulo, Brazil
Carolina Bruno de Sousa
Centre of Marine Sciences, Faculty of Sciences and Technology, Campus of Gambelas, University of Algarve, Faro, Portugal
Katkam N. Gangadhar
Centre of Marine Sciences, Faculty of Sciences and Technology, Campus of Gambelas, University of Algarve, Faro, Portugal
Maria João Rodrigues
Centre of Marine Sciences, Faculty of Sciences and Technology, Campus of Gambelas, University of Algarve, Faro, Portugal
Hugo Pereira
Centre of Marine Sciences, Faculty of Sciences and Technology, Campus of Gambelas, University of Algarve, Faro, Portugal
Raquel T. Lima
i3S—Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Rua Alfredo Allen, Porto, Portugal
M. Helena Vasconcelos
i3S—Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Rua Alfredo Allen, Porto, Portugal
Luísa Barreira
Centre of Marine Sciences, Faculty of Sciences and Technology, Campus of Gambelas, University of Algarve, Faro, Portugal
Amélia P. Rauter
Center of Chemistry and Biochemistry, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Lisbon, Lisbon, Portugal
Fernando Albericio
Institute for Research in Biomedicine of Barcelona, Chemistry and Molecular Pharmacology, Barcelona Science Park, Baldiri Reixac, Barcelona, Spain
João Varela
Centre of Marine Sciences, Faculty of Sciences and Technology, Campus of Gambelas, University of Algarve, Faro, Portugal
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.
