<p>HDAC1/2 Inhibitor Romidepsin Suppresses DEN-Induced Hepatocellular Carcinogenesis in Mice</p>

• DOI: 10.2147/ott.s250233
• Publication Date: 2020-06-14T22:11:10Z
• Authors: Hara Afaloniati; Katerina Angelopo...; Alexander Giakous...; Alexandros Hardas; Athanasios Pseftogas; Kali Makedou; Athanasios Gargav...; Thomas Goulopoulos; Stavros Iliadis; Vasileios Papadop...; Apostolos Papalois; George Mosialos; Theofilos Poutahidis; Dimitrios Giakous...
• Keywords: Romidepsin; HDAC1

Background: Hepatocellular carcinoma (HCC) is a frequently diagnosed cancer and leading cause of cancer-related death worldwide. Its rapid progression, combined with the limited treatment options at late stages, imposes need for early detection aggressive intervention. Based on knowledge that hepatocarcinogenesis significantly influenced by histone acetylation, we directed our search novel HCC therapeutics among deacetylation inhibitors (HDACi). The aim present study was to investigate effect HDAC1/2 inhibitor Romidepsin in well-established mouse model diethylnitrosamine (DEN)-induced HCC. Materials Methods: C56BL/6 mice were treated critical point 10 months after DEN challenge their livers examined 2 later using histopathology morphometry. Protein levels assessed serum ELISA liver tissues Western blot immunohistochemistry (in-situ detection). Gene expression quantified real-time PCR. Results: suppressed progression. This associated decreased proliferation increased apoptosis cells. cell cycle regulator CK2a , anti-inflammatory molecule PPAR-γ, tumor suppressors PTEN CYLD upregulated By contrast, PI3K, NF-κB p65 c-Jun reduced. In line this result, two major regulators, ie, BAD multifunctional protein c-Met, lower blood compared untreated Conclusion: These findings suggest Romidepsin, drug currently used lymphoma, could also be considered management early-stage Keywords: diethylnitrosamine, DEN, deacetylases, HDAC, HDAC inhibitors, HDACi, hepatocellular carcinoma, HCC,