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Article

Diallyl trisulfide induces apoptosis by suppressing NF-κB signaling through destabilization of TRAF6 in primary effusion lymphoma

  • Authors:
    • Zenpei Shigemi
    • Yoshiki Furukawa
    • Kohei Hosokawa
    • Setsuya Minami
    • Jumpei Matsuhiro
    • Shiori Nakata
    • Tadashi Watanabe
    • Hiroki Kagawa
    • Koji Nakagawa
    • Hiroshi Takeda
    • Masahiro Fujimuro
  • View Affiliations / Copyright

    Affiliations: Department of Cell Biology, Kyoto Pharmaceutical University, Yamashinaku, Kyoto 607-8412, Japan, Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kitaku, Sapporo 060-0812, Japan
  • Pages: 293-304
    |
    Published online on: November 17, 2015
       https://doi.org/10.3892/ijo.2015.3247
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Abstract

The allyl sulfides, including diallyl sulfide (DAS), diallyl disulfide (DAD), and diallyl trisulfide (DAT), contained in garlic and members of the Allium family, have a variety of pharmacological activities. Therefore, allyl sulfides have been evaluated as potential novel chemotherapeutic agents. Here, we found that DAT inhibited nuclear factor-κB (NF-κB) signaling and induced apoptosis in primary effusion lymphoma (PEL), a subtype of non-Hodgkin's B-cell lymphoma caused by Kaposi's sarcoma-associated herpesvirus (KSHV). We examined the cytotoxic effects of DAS, DAD and DAT on PEL cells. DAT significantly reduced the viability of PEL cells compared with uninfected B-lymphoma cells, and induced the apoptosis of PEL cells by activating caspase-9. DAT induced stabilization of IκBα, and suppressed NF-κB transcriptional activity in PEL cells. We examined the mechanism underlying DAT-mediated IκBα stabilization. The results indicated that DAT stabilized IκBα by inhibiting the phosphorylation of IκBα by the IκB kinase (IKK) complex. Furthermore, DAT induced proteasomal degradation of TRAF6, and DAT suppressed IKKβ-phosphorylation through downregulation of TRAF6. It is known that activation of NF-κB is essential for survival of PEL cells. In fact, the NF-κB inhibitor BAY11-7082 induced apoptosis in PEL cells. In addition, DAT suppressed the production of progeny virus from PEL cells. The administration of DAT suppressed the development of PEL cells and ascites in SCID mice xenografted with PEL cells. These findings provide evidence that DAT has antitumor activity against PEL cells in vitro and in vivo, suggesting it to be a novel therapeutic agent for the treatment of PEL.
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Copy and paste a formatted citation
Spandidos Publications style
Shigemi Z, Furukawa Y, Hosokawa K, Minami S, Matsuhiro J, Nakata S, Watanabe T, Kagawa H, Nakagawa K, Takeda H, Takeda H, et al: Diallyl trisulfide induces apoptosis by suppressing NF-κB signaling through destabilization of TRAF6 in primary effusion lymphoma. Int J Oncol 48: 293-304, 2016.
APA
Shigemi, Z., Furukawa, Y., Hosokawa, K., Minami, S., Matsuhiro, J., Nakata, S. ... Fujimuro, M. (2016). Diallyl trisulfide induces apoptosis by suppressing NF-κB signaling through destabilization of TRAF6 in primary effusion lymphoma. International Journal of Oncology, 48, 293-304. https://doi.org/10.3892/ijo.2015.3247
MLA
Shigemi, Z., Furukawa, Y., Hosokawa, K., Minami, S., Matsuhiro, J., Nakata, S., Watanabe, T., Kagawa, H., Nakagawa, K., Takeda, H., Fujimuro, M."Diallyl trisulfide induces apoptosis by suppressing NF-κB signaling through destabilization of TRAF6 in primary effusion lymphoma". International Journal of Oncology 48.1 (2016): 293-304.
Chicago
Shigemi, Z., Furukawa, Y., Hosokawa, K., Minami, S., Matsuhiro, J., Nakata, S., Watanabe, T., Kagawa, H., Nakagawa, K., Takeda, H., Fujimuro, M."Diallyl trisulfide induces apoptosis by suppressing NF-κB signaling through destabilization of TRAF6 in primary effusion lymphoma". International Journal of Oncology 48, no. 1 (2016): 293-304. https://doi.org/10.3892/ijo.2015.3247
Copy and paste a formatted citation
x
Spandidos Publications style
Shigemi Z, Furukawa Y, Hosokawa K, Minami S, Matsuhiro J, Nakata S, Watanabe T, Kagawa H, Nakagawa K, Takeda H, Takeda H, et al: Diallyl trisulfide induces apoptosis by suppressing NF-κB signaling through destabilization of TRAF6 in primary effusion lymphoma. Int J Oncol 48: 293-304, 2016.
APA
Shigemi, Z., Furukawa, Y., Hosokawa, K., Minami, S., Matsuhiro, J., Nakata, S. ... Fujimuro, M. (2016). Diallyl trisulfide induces apoptosis by suppressing NF-κB signaling through destabilization of TRAF6 in primary effusion lymphoma. International Journal of Oncology, 48, 293-304. https://doi.org/10.3892/ijo.2015.3247
MLA
Shigemi, Z., Furukawa, Y., Hosokawa, K., Minami, S., Matsuhiro, J., Nakata, S., Watanabe, T., Kagawa, H., Nakagawa, K., Takeda, H., Fujimuro, M."Diallyl trisulfide induces apoptosis by suppressing NF-κB signaling through destabilization of TRAF6 in primary effusion lymphoma". International Journal of Oncology 48.1 (2016): 293-304.
Chicago
Shigemi, Z., Furukawa, Y., Hosokawa, K., Minami, S., Matsuhiro, J., Nakata, S., Watanabe, T., Kagawa, H., Nakagawa, K., Takeda, H., Fujimuro, M."Diallyl trisulfide induces apoptosis by suppressing NF-κB signaling through destabilization of TRAF6 in primary effusion lymphoma". International Journal of Oncology 48, no. 1 (2016): 293-304. https://doi.org/10.3892/ijo.2015.3247
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