Cancer-suppressive effect of RNase A and DNase I

Shklyaeva, O. A.; Миронова, Н. Л.; Malkova, E. M.; Taranov, Oleg S.; Ryabchikova, E. I.; Zenkova, Marina A.; Власов, В. В.

doi:10.1134/s1607672908030034

Cited by 14 publications

(14 citation statements)

References 13 publications

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“…1B). Similar results occurred using a Lewis lung carcinoma model, with significant reduction in metastasis and significant increases in survival in response to DNase I injection (38,39). The DNase treatments also were correlated with a reduction in plasma exDNA levels and an increase in plasma DNase levels (Table 1).…”

Section: Dnase Effects On Cancersupporting

confidence: 66%

“…This concept provides a new basis for interpreting long-standing observations that increased exDNA (also called circulating free DNA or cfDNA), and reduced DNase levels in human blood occur in correlation with cancer development and progression (25)(26)(27)(28)(29)(30)(31)(32)(33). Studies by independent laboratories around the world, moreover, repeatedly have documented that DNase 1 added to diverse cancer cells inhibits their metastatic potential (30,(34)(35)(36)(37)(38)(39)(40)(41).…”

Section: Introductionmentioning

confidence: 99%

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Extracellular DNA: A Bridge to Cancer

2015

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DNase I is a secreted enzyme whose function has been presumed to control "waste management" in the human system, by degrading DNA that leaks from dead and dying cells. Emerging studies have instead yielded evidence that DNase I plays a central role in newly defined dynamics of immune and autoimmune diseases, as well as cancer and vascular disorders, including thrombosis. Cancer cells have been reported to be associated with distinctive extracellular structures that facilitate aggregation and implantation. The fact that DNA is a component of such structures and that it plays a role in cancer development is illustrated by direct evidence: DNase I added to tumor cells eliminates the structures and inhibits tumorigenicity of some cancer cell lines. DNase I injected into experimental animals, moreover, results in significant inhibition of metastasis. Despite independent observations of such phenomena in diverse cancers for over 50 years, the potential for using DNase I as a clinical tool to prevent or treat cancer remains unexplored. The discovery of neutrophil extracellular traps has yielded a conceptual framework for interpreting how extracellular DNA may function in cancer development and why it may prove to be an important clinical target in stopping cancer outside the cell. Cancer Res; 75(20);

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Section: Dnase Effects On Cancersupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Extracellular DNA: A Bridge to Cancer

2015

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“…For instance, accumulation of DNA or DNA-protein complexes in the blood causes several autoimmune diseases [5,6]. This accumulation on blood vessel walls, glomeruli, or joints leads to glomerular nephritis, arthritis, or anthema [7].…”

Section: Characteristics Of Nucleasesmentioning

confidence: 99%

“…Thus, RNase A is an important target for drug discovery. RNase is also a candidate disease marker for ovarian tumors and thyroid and pancreatic cancer [4,5]. …”

Section: Characteristics Of Nucleasesmentioning

confidence: 99%

Highly Sensitive Nuclease Assays Based on Chemically Modified DNA or RNA

Sato

Takenaka

2014

Sensors

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Nucleolytic enzymes are associated with various diseases, and several methods have been developed for their detection. DNase expression is modulated in such diseases as acute myocardial infarction, transient myocardial ischemia, oral cancer, stomach cancer, and malignant lymphoma, and DNase I is used in cystic fibroma therapy. RNase is used to treat mesothelial cancer because of its antiproliferative, cytotoxic, and antineoplastic activities. Angiogenin, an angiogenic factor, is a member of the RNase A family. Angiogenin inhibitors are being developed as anticancer drugs. In this review, we describe fluorometric and electrochemical techniques for detecting DNase and RNase in disease. Oligonucleotides having fluorescence resonance energy transfer (FRET)-causing chromophores are non-fluorescent by themselves, yet become fluorescent upon cleavage by DNase or RNase. These oligonucleotides serve as a powerful tool to detect activities of these enzymes and provide a basis for drug discovery. In electrochemical techniques, ferrocenyl oligonucleotides with or without a ribonucleoside unit are used for the detection of RNase or DNase. This technique has been used to monitor blood or serum samples in several diseases associated with DNase and RNase and is unaffected by interferents in these sample types.

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“…It has been shown that the application of RNases as antitumor therapeutics helps to counterbalance the pathological molecular changes that occur within tumor cells and, thus, to control their malignant behavior. The antitumor and antimetastatic activity, as well as general system effects, of natural RNases have been demonstrated (e.g., BS-RNase from bovine testis [ 4 - 7 ], onconase from oocytes of Rana pipiens [ 8 - 10 ], bovine pancreatic RNase A [ 11 - 13 ], and microbial RNases [ 14 - 17 ]). The antitumor effects of Onconase [ 18 , 19 ] and RNase A [ 20 ] were shown to be associated with an alteration in miRNA profiles in tumor cells.…”

Section: Introductionmentioning

confidence: 99%

The systemic tumor response to RNase A treatment affects the expression of genes involved in maintaining cell malignancy

et al. 2017

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Recently, pancreatic RNase A was shown to inhibit tumor and metastasis growth that accompanied by global alteration of miRNA profiles in the blood and tumor tissue (Mironova et al., 2013). Here, we performed a whole transcriptome analysis of murine Lewis lung carcinoma (LLC) after treatment of tumor-bearing mice with RNase A. We identified 966 differentially expressed transcripts in LLC tumors, of which 322 were upregulated and 644 were downregulated after RNase A treatment. Many of these genes are involved in signaling pathways that regulate energy metabolism, cell-growth promoting and transforming activity, modulation of the cancer microenvironment and extracellular matrix components, and cellular proliferation and differentiation. Following RNase A treatment, we detected an upregulation of carbohydrate metabolism, inositol phosphate cascade and oxidative phosphorylation, re-arrangement of cell adhesion, cell cycle control, apoptosis, and transcription. Whereas cancer-related signaling pathways (e.g., TGF-beta, JAK/STAT, and Wnt) were downregulated following RNase A treatment, as in the case of the PI3K/AKT pathway, which is involved in the progression of non-small lung cancer. RNase A therapy resulted in the downregulation of genes that inhibit the biogenesis of some miRNAs, particularly the let-7 miRNA family.Taken together, our data suggest that the antitumor activity and decreased invasion potential of tumor cells caused by RNase A are associated with enhanced energy cascade functioning, rearrangement of cancer-related events regulating cell growth and dissemination, and attenuation of signaling pathways having tumor-promoting activity. Thus, RNase A can be proposed as a potential component of anticancer therapy with multiple modes of action.

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Cancer-suppressive effect of RNase A and DNase I

Cited by 14 publications

References 13 publications

Extracellular DNA: A Bridge to Cancer

Extracellular DNA: A Bridge to Cancer

Highly Sensitive Nuclease Assays Based on Chemically Modified DNA or RNA

The systemic tumor response to RNase A treatment affects the expression of genes involved in maintaining cell malignancy

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