Diethyldithiocarbamate induces apoptosis in HHV-8-infected primary effusion lymphoma cells via inhibition of the NF-κB pathway

  • Authors:
    • Takashi Matsuno
    • Ryusho Kariya
    • Shuichiro Yano
    • Saori Morino-Koga
    • Manabu Taura
    • Mary Ann Suico
    • Yuichiro Shimauchi
    • Shingo Matsuyama
    • Yuka Okamoto
    • Tsuyoshi Shuto
    • Hirofumi Kai
    • Seiji Okada
  • View Affiliations

  • Published online on: December 20, 2011     https://doi.org/10.3892/ijo.2011.1313
  • Pages: 1071-1078
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Abstract

Primary effusion lymphoma (PEL) is a subtype of B-cell lymphoma caused by human herpes virus 8/Kaposi sarcoma-associated herpes virus (HHV-8/KSHV), which is mostly found in patients with AIDS and has poor prognosis. Nuclear factor (NF)-κB pathway is constitutively activated in HHV-8-infected PEL cells and plays a crucial role in tumorigenesis. Recently, it has been shown that diethyldithiocarbamate (DDTC), an active metabolite of disulfiram, has apoptotic activity in cancer cells. Here, we investigated the effect of DDTC on PEL using a PEL mouse model generated by intraperitoneal injection of BC-3 cells, a PEL cell line. DDTC ameliorated the symptoms of PEL in these mice, such as development of ascites, splenomegaly and increase of body weight, in comparison with PBS-treated controls. Moreover, we determined in vitro that DDTC suppressed the constitutively activated NF-κB pathway in BC-3 cells. Methylthiotetrazole assay revealed that the cell proliferation of various PEL cell lines was significantly suppressed by the treatment of DDTC. DDTC also induced the expression of cleaved caspase-3, an apoptosis marker, whereas the addition of Q-VD-OPh, a pan-caspase inhibitor, inhibited cell apoptosis induced by DDTC treatment. Together, our results indicated that DDTC induces apoptosis via inhibition of the NF-κB signaling pathway in HHV-8-infected PEL cells. This study suggests the potential use of DDTC as a therapeutic approach for PEL.
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April 2012
Volume 40 Issue 4

Print ISSN: 1019-6439
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Spandidos Publications style
Matsuno T, Kariya R, Yano S, Morino-Koga S, Taura M, Suico MA, Shimauchi Y, Matsuyama S, Okamoto Y, Shuto T, Shuto T, et al: Diethyldithiocarbamate induces apoptosis in HHV-8-infected primary effusion lymphoma cells via inhibition of the NF-κB pathway. Int J Oncol 40: 1071-1078, 2012
APA
Matsuno, T., Kariya, R., Yano, S., Morino-Koga, S., Taura, M., Suico, M.A. ... Okada, S. (2012). Diethyldithiocarbamate induces apoptosis in HHV-8-infected primary effusion lymphoma cells via inhibition of the NF-κB pathway. International Journal of Oncology, 40, 1071-1078. https://doi.org/10.3892/ijo.2011.1313
MLA
Matsuno, T., Kariya, R., Yano, S., Morino-Koga, S., Taura, M., Suico, M. A., Shimauchi, Y., Matsuyama, S., Okamoto, Y., Shuto, T., Kai, H., Okada, S."Diethyldithiocarbamate induces apoptosis in HHV-8-infected primary effusion lymphoma cells via inhibition of the NF-κB pathway". International Journal of Oncology 40.4 (2012): 1071-1078.
Chicago
Matsuno, T., Kariya, R., Yano, S., Morino-Koga, S., Taura, M., Suico, M. A., Shimauchi, Y., Matsuyama, S., Okamoto, Y., Shuto, T., Kai, H., Okada, S."Diethyldithiocarbamate induces apoptosis in HHV-8-infected primary effusion lymphoma cells via inhibition of the NF-κB pathway". International Journal of Oncology 40, no. 4 (2012): 1071-1078. https://doi.org/10.3892/ijo.2011.1313