Enzyme Activities Controlling Adenosine Levels in Normal and Neoplastic Tissues

Abstract

Adenosine is known to be associated with effects such as inhibition of immune response, coronary vasodilation, stimulation of angiogenesis, and inhibition of inflammatory reactions. Some authors suggest that adenosine may also have similar functions in tumor tissues. Tissue levels of adenosine are under close regulation by different enzymes acting at different levels. Adenosine is produced from AMP by the action of 5'-nucleotidase (5'-NT) and is converted back into AMP by adenosine kinase (AK) or into inosine by adenosine deaminase (ADA). Inosine is converted into purine catabolites by purine nucleoside phosphorylase (PNP), whereas AMP is converted into ADP and ATP by adenylate kinase (MK). The aim of this study was to analyze the activities of the above enzymes in fragments of neoplastic and apparently normal mucosa, obtained less than 5 cm and at least 10 cm from tumors, in 40 patients with colorectal cancer. The results showed much higher activities of ADA, AK, 5'-NT, and PNP in tumor tissue than in neighboring mucosa (p > 0.01 for ADA, AK, and PNP; p > 0.05 for 5'-NT), suggesting that the activities of purine metabolizing enzymes increase to cope with accelerated purine metabolism in cancerous tissue. The simultaneous increase in ADA and 5'-NT activities might be a physiological attempt by cancer cells to provide more substrate to accelerate salvage pathway activity.

7-(2-Thienyl)-7-Deazaadenosine (AB61), a New Potent Nucleoside Cytostatic with a Complex Mode of Action

“…Our further results demonstrated that AB61 is phosphorylated in HCT116 colon cancer cell line (cytotoxicity IC 50 ¼ 1.9 nmol/L) but the phosphorylation does not proceed in normal BJ fibroblasts (cytotoxicity IC 50 ¼ 8 mmol/L). These data are in accordance with the fact that expression of adenosine kinase, the enzyme that might be involved in the phosphorylation of AB61, is increased in colorectal tumors compared with the normal tissue (33)(34)(35). These findings reveal the importance of intracellular phosphorylation for both the efficiency and cancer selectivity of AB61 and suggests for potentially synergistic combinations with therapies increasing nucleoside phosphorylation rates in tumors, for example, radiation (36).…”

Diagnostic Utility of Adenosine Deaminase in Serum and Bronchoalveolar Lavage Fluid for Screening Lung Cancer in Western Iran

“…Several studies investigated the change of the adenosine deaminase activity in various cancerous patients. Many authors have shown the increase of serum tADA activity in these patients (4,7,(23)(24)(25)(26). Adapted to previous data, our results showed higher ADA activity in patients with lung cancer compared to controls.…”

Adenosine deaminase activity in patients with ovarian neoplasms

“…Biri et al [14] demonstrated that decreased activities of ADA in prostate cancer tissue compared with normal prostate tissue. Vannoni et al [15] found very high activities of ADA in colorectal carcinoma as compared with normal colonic mucosa. Aghaei et al [16] studied total ADA and its isoenzyme (ADA-1 and ADA-2) activities in serum, benign and malignant breast tissues and they showed that ADA activities of patients with breast cancer were significantly higher than benign group and healthy subjects.…”

“…High ADA activity in malignant tumors may give selective advantage to the cancer cells via production of hypoxanthine guanine phosphoribosyl transferase (HGPRT). This is a key enzyme for the salvage pathway [15]. In recent years there has been expanding interest in the use of some antigens, hormones, and enzymes for the diagnosis of malign tumors and also for the assessment to the response to treatment.…”