In vitro induction of apoptosis for nasal angiocentric natural killer cell lymphoma-derived cell line, NK-YS, by etoposide and cyclosporine A

Masatoshi Uno, Junjiroh Tsuchiyama, Akiyoshi Moriwaki, Toshio Noguchi, Kazuhiro Mizoguchi, Tetsuya Ogino, Tadashi Yoshino, Shigeru Okada, Mine Harada

Research output: Contribution to journalArticle

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Abstract

Epstein-Barr virus (EBV)-associated nasal T/ natural killer (NK) cell lymphoma has often been reported in Asian countries and has been recently confirmed as a novel clinicopathological entity. The prognosis of advanced stage disease is quite poor and an effective chemotherapeutic modality is strongly advocated. We have established the novel cell line NK-YS, which preserves the original characteristics of EBV-associated nasal angiocentric T/NK cell lymphoma. Using this cell line, we investigated the induction of apoptosis by apoptosis-inducing agents, and expression of P-glycoprotein (P-gp), p53 and bcl-2 proteins. NK-YS showed resistance towards apoptosis-inducing agents and expressed bcl-2 and P-gp but not p53. To overcome this drug resistance, we added cyclosporine A (GSA) and these agents to culture media as a P-gp antagonist. The combination of GsA and etoposide or GsA and doxorubicin induced apoptotic cell death. These results indicated that P-gp-mediated drug resistance is an essential mechanism of drug resistance of the NK-YS cell line. Combined therapy of conventional anti-cancer agents with GsA may have an important place in the establishment of a curative therapy for disseminated nasal angiocentric NK cell lymphoma.

Original languageEnglish
Pages (from-to)1009-1014
Number of pages6
JournalBritish Journal of Haematology
Volume113
Issue number4
DOIs
Publication statusPublished - 2001

Fingerprint

P-Glycoprotein
Etoposide
Nose
Drug Resistance
Natural Killer Cells
Cyclosporine
Lymphoma
Natural Killer T-Cells
Apoptosis
Human Herpesvirus 4
Cell Line
Essential Drugs
Doxorubicin
Culture Media
Cell Death
Therapeutics
In Vitro Techniques
Neoplasms
Proteins

Keywords

  • Chemotherapy
  • Cyclosporine A
  • Drug resistance
  • NK cell
  • P-glycoprotein

ASJC Scopus subject areas

  • Hematology

Cite this

In vitro induction of apoptosis for nasal angiocentric natural killer cell lymphoma-derived cell line, NK-YS, by etoposide and cyclosporine A. / Uno, Masatoshi; Tsuchiyama, Junjiroh; Moriwaki, Akiyoshi; Noguchi, Toshio; Mizoguchi, Kazuhiro; Ogino, Tetsuya; Yoshino, Tadashi; Okada, Shigeru; Harada, Mine.

In: British Journal of Haematology, Vol. 113, No. 4, 2001, p. 1009-1014.

Research output: Contribution to journalArticle

Uno, Masatoshi ; Tsuchiyama, Junjiroh ; Moriwaki, Akiyoshi ; Noguchi, Toshio ; Mizoguchi, Kazuhiro ; Ogino, Tetsuya ; Yoshino, Tadashi ; Okada, Shigeru ; Harada, Mine. / In vitro induction of apoptosis for nasal angiocentric natural killer cell lymphoma-derived cell line, NK-YS, by etoposide and cyclosporine A. In: British Journal of Haematology. 2001 ; Vol. 113, No. 4. pp. 1009-1014.
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