ArticleBMC cancer2011
A human ribonuclease induces apoptosis associated with p21WAF1/CIP1 induction and JNK inactivation.
Article in BMC cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 45 citations in OpenAlex.
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- Dinuclear Iron Complexes of Iminopyridine-Based Ligands as Selective Cytotoxins for Tumor Cells and Inhibitors of Cancer Cell Migration.Pharmaceutics · 2022Article
- Barnase-Barstar Pair: Contemporary Application in Cancer Research and Nanotechnology.Molecules (Basel, Switzerland) · 2021Review
- A Nuclear-Directed Ribonuclease Variant Targets Cancer Stem Cells and Inhibits Migration and Invasion of Breast Cancer Cells.Cancers · 2021Article
- Expression and in vitro anticancer activity of Lp16-PSP, a member of the YjgF/YER057c/UK114 protein family from the mushroom Lentinula edodes CArchives of microbiology · 2021Article
- The Selectivity for Tumor Cells of Nuclear-Directed Cytotoxic RNases Is Mediated by the Nuclear/Cytoplasmic Distribution of p27Molecules (Basel, Switzerland) · 2021Article
- Antitumor Effects of Fucoidan Via Apoptotic and Autophagic Induction on HSC-3 Oral Squamous CellCarcinoma.Asian Pacific journal of cancer prevention : APJCP · 2020Article
- Construction of Highly Stable Cytotoxic Nuclear-Directed Ribonucleases.Molecules (Basel, Switzerland) · 2018Article
- Mitogenic activity of Artocarpus lingnanensis lectin and its apoptosis induction in Jurkat T cells.Journal of natural medicines · 2018Article
- A truncated apoptin protein variant selectively kills cancer cells.Investigational new drugs · 2017Article
- Activating transcription factor 3 is crucial for antitumor activity and to strengthen the antiviral properties of Onconase.Oncotarget · 2017Article
- Fucoidan enhances the therapeutic potential of arsenic trioxide and all-trans retinoic acid in acute promyelocytic leukemia, in vitro and in vivo.Oncotarget · 2016Article
- A nuclear-directed human pancreatic ribonuclease (PE5) targets the metabolic phenotype of cancer cells.Oncotarget · 2016Article
- Article
- Killing of cancer cells through the use of eukaryotic expression vectors harbouring genes encoding nucleases and ribonuclease inhibitor.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Review
- A hybrid chimeric system for versatile and ultra-sensitive RNase detection.Scientific reports · 2015Article
- Leczyme: a new candidate drug for cancer therapy.BioMed research international · 2014Review
- Sialic acid-binding lectin (leczyme) induces caspase-dependent apoptosis-mediated mitochondrial perturbation in Jurkat cells.International journal of oncology · 2013Article
- Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid induces apoptosis and cell cycle arrest in CNE-2Z nasopharyngeal carcinoma cells.Oncology reports · 2013Article
- Staphylococcus aureus-induced G2/M phase transition delay in host epithelial cells increases bacterial infective efficiency.PloS one · 2013Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRibonucleases are promising agents for use in anticancer therapy. Among the different ribonucleases described to be cytotoxic, a paradigmatic example is onconase which manifests cytotoxic and cytostatic effects, presents synergism with several kinds of anticancer drugs and is currently in phase II/III of its clinical trial as an anticancer drug against different types of cancer. The mechanism of cytotoxicity of PE5, a variant of human pancreatic ribonuclease carrying a nuclear localization signal, has been investigated and compared to that of onconase.
methodsCytotoxicity was measured by the MTT method and by the tripan blue exclusion assay. Apoptosis was assessed by flow cytometry, caspase enzymatic detection and confocal microscopy. Cell cycle phase analysis was performed by flow cytometry. The expression of different proteins was analyzed by western blot.
resultsWe show that the cytotoxicity of PE5 is produced through apoptosis, that it does not require the proapoptotic activity of p53 and is not prevented by the multiple drug resistance phenotype. We also show that PE5 and onconase induce cell death at the same extent although the latter is also able to arrest the cell growth. We have compared the cytotoxic effects of both ribonucleases in the NCI/ADR-RES cell line by measuring their effects on the cell cycle, on the activation of different caspases and on the expression of different apoptosis- and cell cycle-related proteins. PE5 increases the number of cells in S and G2/M cell cycle phases, which is accompanied by the increased expression of cyclin E and p21WAF1/CIP1 together with the underphosphorylation of p46 forms of JNK. Citotoxicity of onconase in this cell line does not alter the cell cycle phase distribution and it is accompanied by a decreased expression of XIAP
conclusionsWe conclude that PE5 kills the cells through apoptosis associated with the p21WAF1/CIP1 induction and the inactivation of JNK. This mechanism is significantly different from that found for onconase.
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