title: In vitro cytotoxicity of ranpirnase (onconase) in combination with components of R-CHOP regimen against diffuse large B cell lymphoma (DLBCL) cell line.
abstract: Ranpirnase (onconase; ONC) is an endoribonuclease obtained from the frog Rana pipiens. This enzyme exhibits anticancer properties mediated by degradation of cellular RNA and induction of apoptosis. In this study we assessed cytotoxicity of ONC in combination with currently used anticancer drugs on a human diffuse large B-cell lymphoma (DLBCL)-derived cell line (Toledo). Cytotoxic activity was measured by the exclusion of propidium iodide assay while apoptosis was assessed using the annexin-V binding method. Additionally, flow cytometry was used to assess the decline of mitochondrial potential and to determine activation of caspases 3, 8 and 9. It was observed that in vitro treatment with ONC in combination with rituximab, mafosfamide, vincristine, doxorubicin, and dexamethasone (drugs corresponding with elements of R-CHOP regimen) resulted in increased cytotoxicity. As a result ONC showed marked cytotoxicity against Toledo cells. Importantly, in combination of ONC with drugs imitating the R-CHOP regimen, this effect was significantly intensified. The main mechanism responsible for this event was induction of apoptosis along a mitochondrial dependent pathway. In conclusion, these data indicate that further preclinical and eventually clinical studies assessing activity of ONC+R-CHOP treatment are warranted.
authors.affiliation: Department of Experimental Hematology, Medical University of Lodz, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Majchrzak
authors.affiliation: Department of Experimental Hematology and Department of Hematology, Medical University of Lodz, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Witkowska
authors.affiliation: Department of Experimental Hematology, Medical University of Lodz, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Mędra
authors.affiliation: Department of Experimental Hematology and Department of Hematology, Medical University of Lodz, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Zwolińska
authors.affiliation: Department of Experimental Hematology, Medical University of Lodz, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Bogusz
authors.affiliation: Department of Experimental Hematology, Medical University of Lodz, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Cebula-Obrzut
authors.affiliation: The Brander Cancer Research Institute, New York Medical College, Valhalla, NY, USA.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Darzynkiewicz
authors.affiliation: Department of Experimental Hematology, Medical University of Lodz, Poland.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.affiliation: Department of Experimental Hematology, Medical University of Lodz, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Smolewski
mesh_terms: D019268:Antibodies, Antineutrophil Cytoplasmic / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage; D012260:Ribonucleases / Q000008:administration & dosage*; D000069283:Rituximab; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D058846:Antibodies, Monoclonal, Murine-Derived; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D012260:Ribonucleases; D011241:Prednisone; C058703:ranpirnase