Skip to main content

Advertisement

A novel tetrahydrotetramethylbenzophenanthridinone derivative inhibits ATL cell proliferation

Article metrics

  • 750 Accesses

We have previously reported that the tetrahydrotetramethylnaphthalene (TMN) derivative TMNAA is a selective inhibitor of Adult T-cell Leukemia (ATL) and HTLV-1-infected cell lines but not non-ATL cell lines and peripheral blood mononuclear cells (PBMCs). In this study, several derivatives of TMNAA were synthesized and examined for their inhibitory effect on the proliferation of various T cell lines and PBMCs by a tetrazolium dye method. The modes of cell death and cell cycle arrest were also examined by flow cytometry. Among the compounds, MN417 having a tetrahydrotetramethylbenzophenanthridinone structure was found to be a more potent inhibitor of ATL and HTLV-1-infected cell lines than TMNAA. The 50% inhibitory concentrations (IC50s) of MN417 and TMNAA for ATL and HTLV-1-infected cell lines, including S1T and MT-2 cells, were 0.59-6.6 and 2.2-34.2 μM, respectively, depending on the test cell lines. In contrast, the IC50s of MN417 and TMNAA for non-ATL cell lines, such as MOLT-4 and CEM cells, were > 20 and > 100 µM, respectively. The elimination of the TMN moiety from MN417 failed to inhibit the proliferation of ATL and HTLV-1-infected cell lines, suggesting that the TMN moiety was required for the selective inhibition of these cell lines. Furthermore, both MN417 and TMNAA hardly induced apoptosis and cell cycle arrest. Thus, although the target molecule for inhibition of ATL cells remains to be elucidated, the compounds may have potential as novel and selective chemotherapeutic agents ATL.

Author information

Correspondence to Masaaki Toyama.

Rights and permissions

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Reprints and Permissions

About this article

Cite this article

Toyama, M., Takiguchi, J., Aoyama, H. et al. A novel tetrahydrotetramethylbenzophenanthridinone derivative inhibits ATL cell proliferation. Retrovirology 11, P82 (2014) doi:10.1186/1742-4690-11-S1-P82

Download citation

Keywords

  • Cell Death
  • Cell Proliferation
  • Leukemia
  • Infectious Disease
  • Flow Cytometry