Studies on the antiproliferative effects of tropolone derivatives in Jurkat T-lymphocyte cells

• Published in: Bioorganic & medicinal chemistry Vol. 22; no. 7; pp. 2188 - 2193
• Main Authors: Ononye, Sophia N., VanHeyst, Michael D., Giardina, Charles, Wright, Dennis L., Anderson, Amy C.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2014
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Cycle - drug effects; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; HDAC inhibitor; Humans; Jurkat Cells; Leukemia; Leukemia, T-Cell - drug therapy; Leukemia, T-Cell - pathology; Molecular Structure; Natural product; Structure-Activity Relationship; Tropolone; Tropolone - chemical synthesis; Tropolone - chemistry; Tropolone - pharmacology; Tumor Cells, Cultured; Vorinostat; HDAC inhibitor; Natural product; Tropolone; Vorinostat; Leukemia
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2014.02.018

Thujaplicins are tropolone-derived natural products with antiproliferative properties. We recently reported that certain tropolones potently and selectively target histone deacetylases (HDAC) and inhibit the growth of hematological cell lines. Here, we investigated the mechanisms by which these compounds exert their antiproliferative activity in comparison with the pan-selective HDAC inhibitor, vorinostat, using Jurkat T-cell leukemia cells. The tropolones appear to work through a mechanism distinct from vorinostat. These studies suggest that tropolone derivatives may serve as selective epigenetic modulators of hematological cells with potential applications as anti-leukemic or anti-inflammatory agents.