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Cytotoxic activity of the amphibian ribonucleases onconase and r-amphinase on tumor cells from B cell lymphoproliferative disorders.

Authors
  • Smolewski, Piotr
  • Witkowska, Magdalena
  • Zwolinska, Malgorzata
  • Cebula-Obrzut, Barbara
  • Majchrzak, Agata
  • Jeske, Aleksandra
  • Darzynkiewicz, Zbigniew
  • Ardelt, Wojciech
  • Ardelt, Barbara
  • Robak, Tadeusz
Type
Published Article
Journal
International Journal of Oncology
Publisher
Spandidos Publications
Publication Date
Jul 01, 2014
Volume
45
Issue
1
Pages
419–425
Identifiers
DOI: 10.3892/ijo.2014.2405
PMID: 24789756
Source
Medline
License
Unknown

Abstract

Although major advancements in antitumor treatment have been observed, several B cell-derived malignancies still remain incurable. A promising approach that involves targeting RNA either by the use of specific antisense oligonucleotides or cytostatic/cytotoxic ribonucleases (RNases) is being promoted. Two amphibian RNases, onconase (ONC; ranpirnase) and, more recently, r-amphinase (r-Amph), have already been tested, but thus far, mostly on solid tumors. In this study, for the first time we provide comprehensive data on ex vivo and in vivo cytotoxic activity of ONC or r-Amph against cancer cells from different B cell lymphoid malignancies, together with their detailed mode of antitumor action. Our data revealed strong pro-apoptotic activity of ONC and r-Amph in both chronic lymphocytic leukemia and aggressive B cell lymphomas, with less impact on acute lymphoblastic leukemia or multiple myeloma cells. Moreover, the antitumor action of ONC and r-Amph was markedly selective against neoplastic cells sparing normal, healthy control‑derived lymphocytes.

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