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A novel tetramethylnaphthalene derivative synergistically inhibits HTLV-1-infected cell proliferation in combination with cepharanthine

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We have previously found that the novel tetramethylnaphthalene derivative TMNAA selectively inhibits the proliferation of HTLV-1-infected T-cell lines but not HTLV-1-uninfected T-cell lines. Although its target molecule is still unknown, TMNAA did not affect NF-κB activity. Therefore, we further examined the anti-proliferative activity of TMNAA against various T-cell lines in combination with cepharanthine (CEP), which is known to inhibit NF-κB.

Materials and methods

HTLV-1-infected and uninfected T-cell lines were cultured in the presence of various concentrations of TMNAA and CEP, and their proliferation and viability were determined by a tetrazolium dye method. The mode of cell death was also examined by flow cytometry and Western blot analysis.


The 50% inhibitory concentrations (IC50s) of TMNAA and CEP for the ATL cell line (S1T) were 1.65 ± 0.03 and 1.97 ± 0.29 µM, respectively. On the other hand, the IC50 of TMNAA and CEP combination resulted in 0.93 ± 0.13 µM, indicating that the combination synergistically inhibited the proliferation of S1T cells. Such synergism was observed for another infected cell line (MT-2) but not for HTLV-1-uninfected cell lines. Moreover, TMNAA did not induce apoptosis of S1T cells, but CEP did. Interestingly, TMNAA significantly enhanced the CEP-induced apoptosis of S1T and MT-2 cells.


The combination of TMNAA and CEP selectively inhibits the proliferation of HTLV-1-infected cell lines through the induction of apoptosis. Therefore, TMNAA and CEP may have potential for chemotherapy of ATL.

Author information

Correspondence to Masaaki Toyama.

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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 (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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About this article


  • Cell Death
  • Cell Proliferation
  • Western Blot
  • Infectious Disease
  • Blot Analysis