Catarina Vizetto-Duarte1, Luísa Custódio1, Katkam N Gangadhar1, João Henrique G Lago2, Catarina Dias3, Ana Marta Matos3, Nuno Neng3, José Manuel Florêncio Nogueira3, Luísa Barreira1, Fernando Albericio4, Amelia P Rauter3, João Varela5. 1. Centre of Marine Sciences, University of Algarve, Faculty of Sciences and Technology, Ed. 7, Campus of Gambelas, Faro, Portugal. 2. Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of Sao Paulo, 09972-270, Sao Paulo, Brazil. 3. Center 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. 4. Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028, Barcelona, Spain; CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028 Barcelona, Spain; University of Barcelona, Department of Organic Chemistry, Martí i Franqués 1-11, 08028 Barcelona, Spain. 5. Centre of Marine Sciences, University of Algarve, Faculty of Sciences and Technology, Ed. 7, Campus of Gambelas, Faro, Portugal. Electronic address: jvarela@ualg.pt.
Abstract
BACKGROUND: Brown macroalgae have attracted attention because they display a wide range of biological activities, including antitumoral properties. Inthis study we isolated isololiolide from Cystoseira tamariscifolia for the first time. PURPOSE: To examine the therapeutical potential of isololiolide against tumor cell lines. METHODS/STUDY DESIGN: The structure of the compound was established and confirmed by 1D and 2D NMR as well as HRMS spectral analysis. The in vitro cytotoxicity was analyzed by colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in tumoral as well as in non-tumoral cell lines. Cell cycle arrest and induction of apoptosis were assessed by flow cytometry. Alteration of expression levels in proteins important in the apoptotic cascade was analyzed by western blotting. RESULTS: Isololiolidewas isolated for the first time from the brown macroalga C.tamariscifolia. Isololiolide exhibited significant cytotoxic activity against three human tumoral cell lines, namely hepatocarcinoma HepG2 cells, whereas no cytotoxicity was found in non-malignant MRC-5 and HFF-1 human fibroblasts. Isololiolide completely disrupted the HepG2 normal cell cycle and induced significant apoptosis. Moreover, western blot analysis showed that isololiolide altered the expression of proteins that are important in the apoptotic cascade, increasing PARP cleavage and p53 expression while decreasing procaspase-3 and Bcl-2 levels. CONCLUSION: Isololiolide isolated from C. tamariscifolia is able to exert a selective cytotoxic activity on hepatocarcinoma HepG2 cells as well as induce apoptosis through the modulation of apoptosis-related proteins.
BACKGROUND: Brown macroalgae have attracted attention because they display a wide range of biological activities, including antitumoral properties. Inthis study we isolated isololiolide from Cystoseira tamariscifolia for the first time. PURPOSE: To examine the therapeutical potential of isololiolide against tumor cell lines. METHODS/STUDY DESIGN: The structure of the compound was established and confirmed by 1D and 2D NMR as well as HRMS spectral analysis. The in vitro cytotoxicity was analyzed by colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in tumoral as well as in non-tumoral cell lines. Cell cycle arrest and induction of apoptosis were assessed by flow cytometry. Alteration of expression levels in proteins important in the apoptotic cascade was analyzed by western blotting. RESULTS:Isololiolidewas isolated for the first time from the brown macroalga C.tamariscifolia. Isololiolide exhibited significant cytotoxic activity against three humantumoral cell lines, namely hepatocarcinoma HepG2 cells, whereas no cytotoxicity was found in non-malignant MRC-5 and HFF-1 human fibroblasts. Isololiolide completely disrupted the HepG2 normal cell cycle and induced significant apoptosis. Moreover, western blot analysis showed that isololiolide altered the expression of proteins that are important in the apoptotic cascade, increasing PARP cleavage and p53 expression while decreasing procaspase-3 and Bcl-2 levels. CONCLUSION:Isololiolide isolated from C. tamariscifolia is able to exert a selective cytotoxic activity on hepatocarcinoma HepG2 cells as well as induce apoptosis through the modulation of apoptosis-related proteins.
Authors: Katkam N Gangadhar; Maria João Rodrigues; Hugo Pereira; Helena Gaspar; F Xavier Malcata; Luísa Barreira; João Varela Journal: Mar Drugs Date: 2020-11-19 Impact factor: 5.118