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

Smolewski,Piotr; Witkowska,Magdalena; Zwolinska,Malgorzata; Cebula-Obrzut,Barbara; Majchrzak,Agata; Jeske,Aleksandra; Darzynkiewicz,Zbigniew; Ardelt,Wojciech; Ardelt,Barbara; Robak,Tadeusz

doi:10.3892/ijo.2014.2405

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

Authors:
- Piotr Smolewski
- Magdalena Witkowska
- Malgorzata Zwolinska
- Barbara Cebula-Obrzut
- Agata Majchrzak
- Aleksandra Jeske
- Zbigniew Darzynkiewicz
- Wojciech Ardelt
- Barbara Ardelt
- Tadeusz Robak
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Affiliations: Department of Experimental Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland, The Brander Cancer Research Institute, New York Medical College, Valhalla, NY, USA, TAmiR Biotechnology, Inc, Somerset, NJ, USA, Department of Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland
Published online on: April 28, 2014 https://doi.org/10.3892/ijo.2014.2405
Pages: 419-425

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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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