Synergistic Effect of Epigenetic Inhibitors Decitabine and Suberoylanilide Hydroxamic Acid on Colorectal Cancer In vitro

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dc.contributor.author Najem, Sonia A.
dc.contributor.author Khawaja, Ghada
dc.contributor.author Hodroj, Mohammad Hassan
dc.contributor.author Rizk, Sandra
dc.date.accessioned 2019-12-03T11:47:32Z
dc.date.available 2019-12-03T11:47:32Z
dc.date.copyright 2019 en_US
dc.identifier.issn 1874-4702 en_US
dc.identifier.uri http://hdl.handle.net/10725/11599
dc.description.abstract Background: Colorectal Cancer (CRC) is a common cause of oncological deaths worldwide. Alterations of the epigenetic landscape constitute a well-documented hallmark of CRC phenotype. The accumulation of aberrant DNA methylation and histone acetylation plays a major role in altering gene activity and driving tumor onset, progression and metastasis. Objective: In this study, we evaluated the effect of Suberoylanilide Hydroxamic Acid (SAHA), a panhistone deacetylase inhibitor, and Decitabine (DAC), a DNA methyltransferase inhibitor, either alone or in combination, on Caco-2 human colon cancer cell line in vitro. Results: Our results showed that SAHA and DAC, separately, significantly decreased cell proliferation, induced apoptosis and cell cycle arrest of Caco-2 cell line. On the other hand, the sequential treatment of Caco-2 cells, first with DAC and then with SAHA, induced a synergistic anti-tumor effect with a significant enhancement of growth inhibition and apoptosis induction in Caco-2 cell line as compared to cells treated with either drug alone. Furthermore, the combination therapy upregulates protein expression levels of pro-apoptotic proteins Bax, p53 and cytochrome c, downregulates the expression of antiapoptotic Bcl-2 protein and increases the cleavage of procaspases 8 and 9; this suggests that the combination activates apoptosis via both the intrinsic and extrinsic pathways. Mechanistically, we demonstrated that the synergistic anti-neoplastic activity of combined SAHA and DAC involves an effect on PI3K/AKT and Wnt/β-catenin signaling. Conclusion: In conclusion, our results provide evidence for the profound anti-tumorigenic effect of sequentially combined SAHA and DAC in the CRC cell line and offer new insights into the corresponding underlined molecular mechanism. en_US
dc.language.iso en en_US
dc.title Synergistic Effect of Epigenetic Inhibitors Decitabine and Suberoylanilide Hydroxamic Acid on Colorectal Cancer In vitro en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SAS en_US
dc.author.idnumber 199829370 en_US
dc.author.department Natural Sciences en_US
dc.description.embargo N/A en_US
dc.relation.journal Current Molecular Pharmacology en_US
dc.journal.volume 12 en_US
dc.journal.issue 4 en_US
dc.article.pages 281-300 en_US
dc.keywords Apoptosis en_US
dc.keywords Colon cancer en_US
dc.keywords Decitabine en_US
dc.keywords Epigenetics en_US
dc.keywords In vitro en_US
dc.keywords Suberoylanilide hydroxamic acid en_US
dc.identifier.doi https://doi.org/10.2174/1874467212666190313154531 en_US
dc.identifier.ctation Najem, S. A., Khawaja, G., Hodroj, M. H., & Rizk, S. (2019). Synergistic effect of epigenetic inhibitors Decitabine and Suberoylanilide Hydroxamic acid on colorectal Cancer in vitro. Current molecular pharmacology, 12(4), 281-300. en_US
dc.author.email sandra.rizk@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url https://www.fasebj.org/doi/abs/10.1096/fasebj.2019.33.1_supplement.647.38 en_US
dc.orcid.id https://orcid.org/0000-0002-4405-5703 en_US
dc.author.affiliation Lebanese American University en_US

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