In vitro cytotoxicity of ranpirnase (onconase) in combination with components of R-CHOP regimen against diffuse large B cell lymphoma (DLBCL) cell line.
Postepy Hig Med Dosw (Online)
; 67: 1166-72, 2013 Dec 02.
Article
em En
| MEDLINE
| ID: mdl-24379257
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ribonucleases
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Linfoma Difuso de Grandes Células B
/
Anticorpos Anticitoplasma de Neutrófilos
Limite:
Humans
Idioma:
En
Revista:
Postepy Hig Med Dosw (Online)
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
MEDICINA
/
SAUDE PUBLICA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Polônia