Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bovine seminal ribonuclease (BS-RNase) is a homologue of RNase A with specific antitumor activity. The cytotoxic action of this agent was examined in human neuroblastoma (NB) cell lines (SK-N-SH and UKF-NB-4) possessing the multidrug resistance (MDR) phenotype and NB cell lines (IMR-32, UKF-NB-1, UKF-NB-2 and UKF-NB-3) without MDR. Although MDR cells expressed large amounts of mdr-1 mRNA, contained functional P-glycoprotein and had 20- to 105-fold lower sensitivities to doxorubicin and vincristine than cells with non-MDR phenotypes, BS-RNase was equally toxic to all NB cells at concentrations employed (0.2 to 100 microg/ml). BS-RNase showed high selectivity for NB cells and was non-toxic to normal fibroblasts and epithelial cells. Ultrastructural investigation and annexin V assay showed that BS-RNase is a powerful inductor of apoptosis. The antitumoral effects of BS-RNase were also demonstrated in vivo using established subcutaneous xenografts in athymic (nude) mice of the MDR-1-bearing UKF-NB-4 cell line. Intratumoral injections (12.5 mg/kg) of BS-RNase over four weeks resulted in complete tumor regression and absence of tumor regrowth over a two-week observation period after cessation of treatment. The results show that BS-RNase selectively kills NB cells by inducing apoptosis and that this agent is active against mdr-1 expressing cells both in vitro and in vivo. BS-RNase fulfills important criteria for a candidate antitumor agent in NB patients with advanced disease.
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PMID:Bovine seminal ribonuclease selectively kills human multidrug-resistant neuroblastoma cells via induction of apoptosis. 1053 85

Bovine seminal ribonuclease (BS RNase), a dimeric homolog of bovine pancreatic ribonuclease has been proven to have important biological properties as aspermatogenic, antitumor, embryotoxic and immunosuppressive activities. Recently we published preliminary results concerning the ability of bovine seminal ribonuclease (BS RNase) to induce time dependent apoptosis in Con-A stimulated human lymphocytes and in human tumor cells based on DNA content and cell cycle analysis. In this study we bring more confirmative data concerning the concentration dependent in vitro induction of apoptosis in stimulated human lymphocytes and tumor cells of three human cell lines using the most sensitive and specific cytometric method for at present apoptosis determination the indirect TUNEL. BS RNase 50 microg/ml was proven to induce 49.7, 54 and 68.1% apoptosis in the cells of the ML-2 myeloid cell line and two neuroblastoma cell lines: NB-1 and NB-2, respectively. In Con A-stimulated human lymphocytes, BS RNase also induced apoptosis, eventhough not so pronounced as in human tumor cell lines. In all cultures the induction of apoptosis was proportional to BS RNase concentration ranging from 2-50 microg/ml and correlated with proportional decrease in 3H-thymidine incorporation into the newly synthesized DNA. Side by side with the ability of BS RNase to suppress the growth of human tumors transplanted to nude mice, these biological properties determine this enzyme as a promising agent with potential clinical application.
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PMID:Bovine seminal ribonuclease induces in vitro concentration dependent apoptosis in stimulated human lymphocytes and cells from human tumor cell lines. 1113 Feb 46