The role and significance of alpha-lipoic acid and non-steroidal anti-inflammatory drugs in the chemoprevention and induction of apoptotosis in colon and cervix cancer cell lines - in vitro study

[I. D. Damnjanović]

146 listova

Clinical pharmacology

The colon and cervix cancer treatment is usually based on the activity of one or more chemotherapeutic agents, which stop the cell cycle in numerous ways, by showing a high level of adverse effects and the development of resistance. Therefore, finding new or improving the existing agents with potential antitumor activity is imperative in the contemporary pharmacotherapy of cancer. Increasing the efficiency of chemotherapeutic agents can be achieved by combining the treatment with chemopreventive agents, which would enhance the effectiveness of the cytostatics and reduce the side effects. The aim of this study is to investigate the effect of the alpha-lipoic acid, ketoprofen, meloxicam and the combinations of tese test substances with cisplatin and 5-fluorouracil, in the cell cultures of colon and cervical cancer and the primary cultures of the mononuclear cells of peripheral blood, on cell proliferation and the quantitative expression of NF-B, Bcl- 2 and Bax protein in order to assess the test substances’ chemopreventive potential. The MTT test in the cell proliferation assay was used to examine the effect of test substances on the proliferation of colon and cervix cancer cells, while the quantitative expression of the NF-B, Bcl-2 and Bax protein was determined in correspondence to the immunofluorescence method. The role of the mononuclear cells of peripheral blood in the conducted research, is based on monitoring the selectivity of the tested substances by analysing the expression of mitochondrial apoptosis markers. The research results show that the alpha-lipoic acid, ketoprofen and meloxicam have an important role in the chemoprevention of colon and cervix cancer, by having an influence on the expression of NF-B, Bcl-2 and Bax, as important markers of the apoptotic cell power of the colon and cervix cancer cells. The test substances showed a dose-dependent effect, especially in combination with the cytostatics. When it comes to the comparison of the antiiflamatory nonsteroidal drugs, the priority could be given to meloxicam, probably due to the more selective profile of the COX-2 inhibition. The results could be very good candidates for the further in vivo preclinical studies in order to potentiate the effects, in a particular reference to the development of resistance and the reduction of the side effects that occur in the standard cytostatic treatment of colon and cervix cancer

Karcinom kolona, karcinom cerviksa, apoptoza, hemoprevencija, alfalipoinska kiselina, ketoprofen, meloksikam

colon cancer, cervix cancer, apoptosis, chemoprevention, alpha-lipoic acid, ketoprofen, meloxicam

615.03

Tekst