NYMC Faculty Publications

Cytotoxic Activity of the Amphibian Ribonucleases Onconase and r-Amphinase on Tumor Cells From B Cell Lymphoproliferative Disorders

Author Type(s)

Faculty

DOI

10.3892/ijo.2014.2405

Journal Title

International Journal of Oncology

First Page

419

Last Page

425

Document Type

Article

Publication Date

7-1-2014

Department

Pathology, Microbiology and Immunology

Keywords

Adult, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, B-Lymphocytes, Cell Line, Tumor, Dose-Response Relationship, Drug, Doxorubicin, Drug Resistance, Neoplasm, Female, Gene Expression Regulation, Neoplastic, Humans, Lymphoproliferative Disorders, Male, Middle Aged, Ribonucleases, Young Adult

Disciplines

Medicine and Health Sciences

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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