Avaliação do efeito de compostos da classe de 3-triazol-5-fenil-telurotimidina em células de câncer de mama

Abstract

Azido-3-deoxythymidine (AZT) is a nucleoside reverse transcriptase inhibitor with antitumor activity that has been revitalized through the insertion of molecules that potentiate its effect. The objective of this study was to investigate the effect and underlying mechanisms of cell death of AZT and its derivatives on human breast cancer cell lines. This neoplasm is the second most common type of cancer in the world and the most frequent among women. Chemotherapy currently used is often limited mainly due to the toxicity and development of drug resistance. With this problem, researchers have been showing great interest in the use of nucleosides, since they have a wide biological application and a structure favorable to modifications. The inhibitory effect of AZT and its derivatives (1a and 1b) was determined by the MTT assay, flow cytometric analyzes were used to evaluate, induce apoptosis and distribution in the cell cycle. Finally, the effect of combining derivatives 1a and 1b with doxorubicin was also analyzed. The MTT assay showed that AZT derivatives decreased the rate of cell proliferation at concentrations of 12.5 μM in 48 hours, while commercial AZT showed low antitumor potential. In the flow cytometric analysis, it was observed that the AZT derivatives do not induce apoptosis at the concentration tested and promote cell cycle arrest in the S phase. When the derivatives were combined doxorubicin showed a significant increase of the inhibitory effect in the carcinoma cells compared to individual treatments. Therefore, these compounds are potential therapeutic agents for breast cancer.