Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.22.1 (DNase II)
 429 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deficiency of alkaline and acid DNase is a hallmark in all non-necrotic cancer cells in animals and humans. These enzymes are reactivated at early stages of cancer cell death by vitamin C (acid DNase) and vitamin K(3) (alkaline DNase). Moreover, the coadministration of these vitamins (in a ratio of 100:1, for C and K(3), respectively) produced selective cancer cell death. Detailed morphological studies indicated that cell death is produced mainly by autoschizis, a new type of cancer cell death. Several mechanisms are involved in such a cell death induced by CK(3), they included: formation of H(2)O(2) during vitamins redox cycling, oxidative stress, DNA fragmentation, no caspase-3 activation, and cell membrane injury with progressive loss of organelle-free cytoplasm. Changes in the phosphorylation level of some critical proteins leading to inactivation of NF-kappaB appear as main intracellular signal transduction pathways. The increase knowledge in the mechanisms underlying cancer cells death by CK(3) may ameliorate the techniques of their in vivo administration. The aim is to prepare the introduction of the association of vitamins C and K(3) into human clinics as a new, non-toxic adjuvant cancer therapy.
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PMID:The association of vitamins C and K3 kills cancer cells mainly by autoschizis, a novel form of cell death. Basis for their potential use as coadjuvants in anticancer therapy. 1276 95

We have previously shown that DNA from dying tumor cells may be transferred to living cells via the uptake of apoptotic bodies and may contribute to tumor progression. DNA encoding H-ras(V12) and c-myc oncogenes may be transferred to the nucleus of the phagocyte but will only integrate and propagate in p53- and p21-deficient mouse embryonic fibroblasts, whereas normal cells are resistant to transformation. Here, we show that this protective mechanism (activation of p53 and p21 after uptake of apoptotic bodies) is dependent on DNA fragmentation, where inhibition of the caspase-activated DNase in the apoptotic cells, in conjunction with genetic ablation of lysosomal DNase II in the phagocytes, completely blocks p53 activation and consequently allows DNA replication of transferred DNA. We, therefore, suggest that there is a causal relationship between DNA degradation during apoptosis and p53 activation. In addition, we could further show that Chk2-/- cells were capable of replicating the hyg(R) gene taken up from engulfed apoptotic cells, suggesting involvement of the DNA damage response. These data show that the phagocytosing cell is sensing the degraded DNA within the apoptotic cell, hence preventing these genes from being replicated, probably through activation of the DNA damage response. We, therefore, hypothesize that DNase II together with the Chk2, p53, and p21 pathway form a genetic barrier blocking the replication of potentially harmful DNA introduced via apoptotic bodies, thereby preventing transformation and malignant development.
Mol Cancer Res 2006 Mar
PMID:DNase II and the Chk2 DNA damage pathway form a genetic barrier blocking replication of horizontally transferred DNA. 1654 56

The alterations of deoxyribonuclease DNase activity in cancer cells were the basis of the utilization of mixed vitamins C and K3 in a nontoxic, adjuvant cancer therapy. In order to localize exactly the altered activities of DNase in cancer cells, histochemical methods were utilized. The deficiency of alkaline and acid DNase activity appeared to be characteristic for non-necrotic cells of malignant human and animal tumors. This enzymatic deficiency appeared in experimental carcinogenesis before the phenotypic signs of malignancy. Tumor promoters directly reduced the activity of both DNases. The incidence of spontaneous malignant human and animal tumors appeared to be inversely proportional to the intensity of the activity of both DNases in normal cells and tissues from which these tumors were derived. The fact that alkaline and acid DNase activity was reactivated during the spontaneous and therapeutically induced necrosis of cancer cells suggests that this enzymatic deficiency of DNase activity in cancer cells was due to the action of specific inhibitors of DNases. Characteristic variations of serum alkaline DNase activity in positive responders to therapy, examined in more than 800 cancer-bearing patients, may be the basis for the development of a useful test for therapeutic prognosis and for monitoring of cancer bearing patients. Acid DNase was selectively reactivated in malignant tumor cells by vitamin C (sodium ascorbate), whereas alkaline DNase was reactivated by vitamin K3. Joint vitamin C and K3 administration produced in vitro and in vivo tumor growth inhibition, potentiation and sensitization of chemo- and/or radiotherapy and a decrease in the number of metastases in animals with experimental tumors. Joint vitamin C and K3 administration may be considered as a possible new, non-toxic, adjuvant cancer therapy, which can be easily introduced into the classic protocols of clinical cancer therapy without any supplementary risk for patients.
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PMID:Altered deoxyribonuclease activity in cancer cells and its role in non toxic adjuvant cancer therapy with mixed vitamins C and K3. 1903 2

Programmed cell death is an important factor in tissue homeostasis. Lot of work has been performed to characterize the caspase-dependent cell death. Caspase-independent cell death, although important in many physiological situations, is less investigated. In this work we show that two caspase-independent effectors of cell death, namely apoptosis-inducing factor and leukocyte elastase inhibitor derived DNase II interact and can cooperate to induce cell death. These results contribute to the knowledge of molecular pathways of cell death, an important issue in the development of new therapeutic strategies for the treatment of cancer or neurodegenerative diseases.
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PMID:Apoptosis-inducing factor (AIF) and leukocyte elastase inhibitor/L-DNase II (LEI/LDNaseII), can interact to conduct caspase-independent cell death. 2367 89

Amiloride derivatives are a class of new promising chemotherapeutic agents. A representative member of this family is the sodium-hydrogen antiporter inhibitor HMA (5-(N,N-hexamethylene amiloride), which has been demonstrated to induce cellular intracytosolic acidification and cell death through the apoptotic pathway(s). This work aims at characterizing drug response of human cancer cell lines to HMA. After a first screening revealing that HMA interferes with cancer cell survival, we focused our attention on SW613-B3 colon carcinoma cells, which are intrinsically resistant to a panel of drugs. Searching for the activation of canonical apoptosis, we found that this process was abortive, given that the final steps of this process, i.e. PARP-1 cleavage and DNA ladder, were not detectable. Thus, we addressed caspase-independent paradigms of cell death and we observed that HMA promotes the induction of the LEI/L-DNase II pathway as well as of parthanatos. Finally, we explored the possible impact of autophagy of cell response to HMA, providing the evidence that autophagy is activated in our experimental system. On the whole, our results defined the biochemical reactions triggered by HMA, and elucidated its multiple effects, thus adding further complexity to the intricate network leading to drug resistance.
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PMID:Multiple effects of the Na(+)/H (+) antiporter inhibitor HMA on cancer cells. 2399 9


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