BIBLIOS

Document type
Journal articles

Document subtype
Full paper

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 cleavage

Participants in the publication
Catarina Vizetto-Duarte (Author)
Luísa Custódio (Author)
Katkam N. Gangadhar (Author)
João Henrique G. Lago (Author)
Catarina Dias (Author)
Ana Marta Matos (Author)
CQE
Nuno Neng (Author)
Dep. Química e Bioquímica
CQB
José Manuel Florêncio Nogueira (Author)
Dep. Química e Bioquímica
CQB
Luísa Barreira (Author)
Fernando Albericio (Author)
Amelia P. Rauter (Author)
Dep. Química e Bioquímica
CQB
João Varela (Author)

Summary
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\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\nNMR as well as HRMS spectral analysis. The in vitro cytotoxicity was analyzed by colorimetric 3-(4,5-\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\ndimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in tumoral as well as in non-tumoral cell\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\nlines. 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.\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\nResults: Isololiolidewas isolated for the first time from the brown macroalga C.tamariscifolia. Isololiolide\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\nexhibited significant cytotoxic activity against three human tumoral cell lines, namely hepatocarcinoma\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\nHepG2 cells, whereas no cytotoxicity was found in non-malignant MRC-5 and HFF-1 human fibroblasts.\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\nIsololiolide 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\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\nin the apoptotic cascade, increasing PARP cleavage and p53 expression while decreasing procaspase-3 and\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\nBcl-2 levels.\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\nConclusion: Isololiolide isolated from C. tamariscifolia is able to exert a selective cytotoxic activity on\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\nhepatocarcinoma HepG2 cells as well as induce apoptosis through the modulation of apoptosis-related\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\nproteins.


Institution
FACULDADE DE CIÊNCIAS DA UNIVERSIDADE DE LISBOA

Where published
Phytomedicine

Publication Identifiers
ISSN - 0944-7113

Publisher
Elsevier BV



Document Identifiers
DOI - https://doi.org/10.1016/j.phymed.2016.02.008
URL - http://dx.doi.org/10.1016/j.phymed.2016.02.008

Awards
JOurnal ranked in the TOP 4% of the area Complementary and Alternative Medicine
Journal ranked in the TOP 4% of the area Integrative and Complementary Medicine

Rankings
SCIMAGO Q1 (2016) - 1,094 - Drug Discovery
Web Of Science Q1 (2016) - 3.526 - INtegrative and Complementary Medicine

Keywords
Cell cycle Apoptosis Carotenoid metabolite Isololiolide Cystoseira Marine natural product

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