Cytotoxic activity of the amphibian ribonucleases onconase and r-amphinase on tumor cells from B cell lymphoproliferative disorders.
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.
Department of Experimental Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland.
Piotr
P
Smolewski
Department of Experimental Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland.
Magdalena
M
Witkowska
Department of Experimental Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland.
Malgorzata
M
Zwolinska
Department of Experimental Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland.
Barbara
B
Cebula-Obrzut
Department of Experimental Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland.
Agata
A
Majchrzak
Department of Experimental Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland.
Aleksandra
A
Jeske
The Brander Cancer Research Institute, New York Medical College, Valhalla, NY, USA.
Zbigniew
Z
Darzynkiewicz
TAmiR Biotechnology, Inc, Somerset, NJ, USA.
Wojciech
W
Ardelt
TAmiR Biotechnology, Inc, Somerset, NJ, USA.
Barbara
B
Ardelt
Department of Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland.
Tadeusz
T
Robak
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols; D001402:B-Lymphocytes / Q000473:pathology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012260:Ribonucleases / Q000008:administration & dosage* / Q000494:pharmacology; D055815:Young Adult
D000970:Antineoplastic Agents; D004317:Doxorubicin; D012260:Ribonucleases; C522843:amphinase, Rana pipiens; C058703:ranpirnase