Publication Type Journal Article
Title Isololiolide, a carotenoid metabolite isolated from the brown alga Cystoseira tamariscifolia, is cytotoxic and able to induce apoptosis in hepatocarcinoma cells through caspase-3 activation, decreased Bcl-2 levels, increased p53 expression and PARP c
Authors Catarina Vizetto-Duarte Luisa Custodio KatkamN. Gangadhar Joao Henrique G. Lago Catarina Dias Ana Marta Matos Nuno Neng J. M. F. Nogueira Luisa Barreira Fernando Albericio Amélia P. Rauter Joao Varela
Groups HC Chem4Env
Journal PHYTOMEDICINE
Year 2016
Month May
Volume 23
Number 5
Pages 550-557
Abstract Background: Brown macroalgae have attracted attention because they display a wide range of biological activities, including antitumoral properties. In this 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. (C) 2016 Elsevier GmbH. All rights reserved.
DOI http://dx.doi.org/10.1016/j.phymed.2016.02.008
ISBN
Publisher
Book Title
ISSN 0944-7113
EISSN 1618-095X
Conference Name
Bibtex ID ISI:000373824600013
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