Abstract
Since the histone modifying enzymes EZH2 and HDACs control a number of epigenetic-dependent carcinogenic pathways, we designed the first-in-class dual EZH2/HDAC inhibitor 5 displaying (sub)micromolar inhibition against both targets. When tested in several cancer cell lines, the hybrid 5 impaired cell viability at low micromolar level and in leukemia U937 and rhabdomyosarcoma RH4 cells provided G1 arrest, apoptotic induction, and increased differentiation, associated with an increase of acetyl-H3 and acetyl-α-tubulin and a decrease of H3K27me3 levels. In glioblastoma U87 cells, 5 hampered epithelial to mesenchymal transition by increasing the E-cadherin expression, thus proposing itself as a useful candidate for anticancer therapy. © 2020 American Chemical Society.
Original language | English |
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Pages (from-to) | 977-983 |
Number of pages | 7 |
Journal | ACS Med. Chem. Lett. |
Volume | 11 |
Issue number | 5 |
DOIs | |
Publication status | Published - 2020 |
Keywords
- anticancer agent
- Drug discovery
- dual-target inhibitor
- histone deacetylase
- histone methyltransferase
- alpha tubulin
- antineoplastic agent
- histone deacetylase inhibitor
- transcription factor EZH2
- uvomorulin
- alveolar rhabdomyosarcoma cell line
- Article
- biological activity
- cancer cell
- cell differentiation
- cell viability
- controlled study
- drug design
- drug screening
- epithelial mesenchymal transition
- G1 phase cell cycle checkpoint
- glioblastoma cell line
- human
- human cell
- priority journal
- protein expression
- U-937 cell line