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Bortezomib induces apoptosis in T lymphoma cells and natural killer lymphoma cells independent of Epstein‐Barr virus infection
Author(s) -
Iwata Seiko,
Yano Shoko,
Ito Yoshinori,
Ushijima Yoko,
Gotoh Kensei,
Kawada Junichi,
Fujiwara Shigeyoshi,
Sugimoto Koichi,
Isobe Yasushi,
Nishiyama Yukihiro,
Kimura Hiroshi
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25873
Subject(s) - bortezomib , proteasome inhibitor , apoptosis , lymphoma , cancer research , biology , epstein–barr virus , peripheral blood mononuclear cell , immunology , microbiology and biotechnology , virus , multiple myeloma , in vitro , biochemistry
Epstein‐Barr virus (EBV), which infects not only B cells, but also T cells and natural killer (NK) cells, is associated with multiple lymphoid malignancies. Recently, the proteasome inhibitor bortezomib was reported to induce apoptosis of EBV‐transformed B cells. We evaluated the killing effect of this proteasome inhibitor on EBV‐associated T lymphoma cells and NK lymphoma cells. First, we found that bortezomib treatment decreased the viability of multiple T and NK cell lines. No significant difference was observed between EBV‐positive and EBV‐negative cell lines. The decreased viability in response to bortezomib treatment was abrogated by a pan‐caspase inhibitor. The induction of apoptosis was confirmed by flow cytometric assessment of annexin V staining. Additionally, cleavage of caspases and polyadenosine diphosphate‐ribose polymerase, increased expression of phosphorylated IκB, and decreased expression of inhibitor of apoptotic proteins were detected by immunoblotting in bortezomib‐treated cell lines. We found that bortezomib induced lytic infection in EBV‐positive T cell lines, although the existence of EBV did not modulate the killing effect of bortezomib. Finally, we administered bortezomib to peripheral blood mononuclear cells from five patients with EBV‐associated lymphoproliferative diseases. Bortezomib had a greater killing effect on EBV‐infected cells. These results indicate that bortezomib killed T or NK lymphoma cells by inducing apoptosis, regardless of the presence or absence of EBV.