Archives
In our previous study we showed
In our previous study we showed that normal and cancerous A 419259 trihydrochloride of kidney exhibit the activity of alcohol dehydrogenase and aldehyde dehydrogenase. Furthermore, the activity of class I ADH isoenzymes and total ADH were significantly higher in cancer tissue than in unchanged renal cells. Moreover, the activity of ADH seems to be disproportionately high compared to the activity of ALDH, what suggests an increased ability of cancer cells to form the highly toxic and mutagenic acetaldehyde and initiating disorders in metabolism of many biologically important substances [10].
Material and methods
Results
The activities of total ADH, ALDH and ADH isoenzymes in the sera of patients with renal cell carcinoma are presented in Table 1. The total activity of alcohol dehydrogenase was significantly higher (about 26%) in the serum of patients with renal cancer than in healthy subjects. The median total activity of ADH was 1213.0 mIU/l in the RCC group and 895.0 mIU/l in the control group. The analysis of ALDH activity did not indicate significant differences between total tested group and healthy persons.
The comparison of ADH isoenzymes activities showed that the highest difference was exhibited by class I ADH. The median activity of this class of isoenzymes in the cancer group increased by about 24% (1.785 mIU/l) in comparison to the control level (1.338 mIU/l). The increase of ADH I activity was statistically significant. The other tested classes of ADH isoenzymes had higher activities in the serum of patients with cancer but the differences were not statistically significant (p>0.05).
The analysis of particular ADH isoenzymes activities depending on the progression stage of carcinoma, showed the tendency of ADH I activity to increase in accordance with the advance of disease (Fig. 1). Significantly higher ADH class I activity was found in every stage (from II to IV) of cancer compared to the control group. In the stage II of cancer advancement we observed about 20% increase of ADH I activity compared to the control group. In the stage III the increase in class I activity was above 23% and in the IV stage − 26% in comparison to healthy subjects. The activity of total ADH was found to be also significantly higher in patients with renal cancer without dependence on tumor stage. The other isoenzymes did not exhibit any characteristic changes of activity correlating with stage of disease. The total activity of ALDH also did not indicate significant differences between advancement stages.
Discussion
Renal cell carcinoma is characterized by an abnormally high glycogen deposition caused by altered enzyme activities [17]. Many studies reported decreased expression of glucose 6-phosphatase, aminoacylase-I and aldehyde dehydrogenase-1 in RCC [18,19]. ALDH catalyses an oxidation of aldehydes to carboxylic compounds and this reaction is considered as a general detoxification process. Sreerama at al revealed that ALDH-1 take part in the detoxification of chemotherapeutic agents such as cyclophosphamide, so decrease of this enzyme activity can be the reason of disturbances in this process [20].
Aldehyde dehydrogenase has been characterized as a cancer stem cell marker, which plays a key role in various biological processes in tumor, including cell proliferation, invasiveness and chemoresistance. Recent data of Abourbih et al reported that ALDH1 expression did not correlate with primary tumor grade, stage or with the clinical outcome but ALDH1 membrane expression was significantly higher in low stage as compared to high stage of RCC tumors. Interesting is also that metastatic tumors expressed significantly lower amounts of ALDH1 than primary tumors [21]. During disease progression and metastasis, tumor cells lose the expression patterns of the normal epithelium from which they originate, and therefore healthy kidney has been shown to express large amounts of ALDH1. This confirm that metastases may form altered pathways than the primary tumors, which would clarify differences in enzymes expression [21].