Abstract
It is well established that, during development of malignancies, metabolic changes occur, including alterations of enzyme activities and isoenzyme expression. Arginase and nitric oxide (NO) synthase (NOS) are two of those enzymes considered to be involved in tumorigenesis. The goal of this article was to study the involvement of arginase and NOS in the development of different stages of breast cancer. Our results have shown that human serum arginase activity and NO (resp., and NOS activity) and polyamines quantities increased in parallel with cancer stage progression and decreased after neoadjuvant chemotherapy. For breast cancer, the only isoenzyme of arginase expressed in serum before and after chemotherapy was in a cationic form. The data of Lineweaver-Burk plot with a Km value of 2 mM was calculated, which is characteristic for human liver type isoform of arginase. During electrophoresis at pH 8.9, the enzyme exhibited high electrophoretic mobility and was detected near the anode. The presented results demonstrated that arginase in human serum with breast cancer and after chemotherapy is not polymorphic. We suggest that arginase and NOS inhibition has antitumor effects on cancer development, as it can inhibit polyamines and NO levels, a precursor of cancer cell proliferation, metastasis, and tumor angiogenesis.
Highlights
Breast cancer is one of the most common types of cancer accounting for 19% of all cancer-related mortalities in women
Arginase activity and polyamines and nitric oxide (NO) quantities were determined in blood serum of 11 healthy individuals, patients with breast cancer (54 patients, female, stages I–III, 43–66 years old), and 13 patients after chemotherapy (Table 1)
Our studies have shown that, in women from the breast cancer group of stage I, activity of serum arginase was increased by 50%, in the group of stage II by 72.1%, and in the group of stage III by 131.7% compared to the healthy group (11 healthy individuals) (Figure 1)
Summary
Breast cancer is one of the most common types of cancer accounting for 19% of all cancer-related mortalities in women. It is important to continue improving current diagnostic and treatment tools and to determine new prognostic variables. Research over the last years has convincingly demonstrated an important role for arginase and nitric oxide (NO) synthase (NOS) in tumor immunobiology [1, 2]. Earlier reports focused on the expression of arginase and NOS in murine or human primary cancer tissue as well as malignant cell lines and emphasized its potential role in the promotion of tumor growth via polyamine synthesis or downregulation of NO-mediated tumor cytotoxicity [3, 4]. L-Arginine is used as a substrate by both NOS and arginase to produce NO and urea, respectively.
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