In vitro cytotoxicity of ranpirnase (onconase) in combination with components of R-CHOP regimen against diffuse large B cell lymphoma (DLBCL) cell line
Journal Title: Advances in Hygiene and Experimental Medicine - Year 2013, Vol 67, Issue 0
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 and Affiliations
Agata Majchrzak, Magdalena Witkowska, Aleksandra Mędra, Małgorzata Zwolińska, Jakub Bogusz, Barbara Cebula-Obrzut, Zbigniew Darzynkiewicz, Tadeusz Robak, Piotr Smolewski
Keywords
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