ArticleOncotarget2016
Discovery and characterization of Isofistularin-3, a marine brominated alkaloid, as a new DNA demethylating agent inducing cell cycle arrest and sensitization to TRAIL in cancer cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 60 citations in OpenAlex.
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- Role and mechanism of DNA methylation and its inhibitors in hepatic fibrosis.Frontiers in genetics · 2023Review
- Natural Bioactive Compounds Targeting Histone Deacetylases in Human Cancers: Recent Updates.Molecules (Basel, Switzerland) · 2022Review
- Recent progress in DNA methyltransferase inhibitors as anticancer agents.Frontiers in pharmacology · 2022Review
- Cancer and apoptosis: The apoptotic activity of plant and marine natural products and their potential as targeted cancer therapeutics.Frontiers in pharmacology · 2022Review
- Pharmacological Activities of Extracts and Compounds Isolated from Mediterranean Sponge Sources.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Natural Bioactive Compounds Targeting Epigenetic Pathways in Cancer: A Review on Alkaloids, Terpenoids, Quinones, and Isothiocyanates.Nutrients · 2021Review
- Marine Alkaloids: Compounds with In Vivo Activity and Chemical Synthesis.Marine drugs · 2021Review
- Epigenetic Deregulation of Apoptosis in Cancers.Cancers · 2021Review
- Bioactive Bromotyrosine Derivatives from the Pacific Marine SpongeMarine drugs · 2021Article
- Marine biomimetics: bromotyrosines loaded chitinous skeleton as source of antibacterial agents.Applied physics. A, Materials science & processing · 2021Article
- DNA methylation inhibitors: Retrospective and perspective view.Advances in cancer research · 2021Article
- Advanced Computational Methodologies Used in the Discovery of New Natural Anticancer Compounds.Frontiers in pharmacology · 2021Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We characterized the brominated alkaloid Isofistularin-3 (Iso-3), from the marine sponge Aplysina aerophoba, as a new DNA methyltransferase (DNMT)1 inhibitor. Docking analysis confirmed our in vitro DNMT inhibition data and revealed binding of Iso-3 within the DNA binding site of DNMT1. Subsequent increased expression of tumor suppressor gene aryl hydrocarbon receptor (AHR) could be correlated to decreased methylation of CpG sites within the essential Sp1 regulatory region of its promoter. Iso-3 induced growth arrest of cancer cells in G0/G1 concomitant with increased p21 and p27 expression and reduced cyclin E1, PCNA and c-myc levels. Reduced proliferation was accompanied by morphological changes typical of autophagy revealed by fluorescent and transmission electron microscopy and validated by LC3I-II conversion. Furthermore, Iso-3 strongly synergized with tumor-necrosis-factor related apoptosis inducing ligand (TRAIL) in RAJI [combination index (CI) = 0.22] and U-937 cells (CI = 0.21) and increased TRAIL-induced apoptosis via a mechanism involving reduction of survivin expression but not of Bcl-2 family proteins nor X-linked inhibitor of apoptosis protein (XIAP). Iso-3 treatment decreased FLIPL expression and triggered activation of endoplasmatic reticulum (ER) stress with increased GRP78 expression, eventually inducing TRAIL receptor death receptor (DR)5 surface expression. Importantly, as a potential candidate for further anticancer drug development, Iso-3 reduced the viability, colony and in vivo tumor forming potential without affecting the viability of PBMCs from healthy donors or zebrafish development.
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