Avaliação do potencial citotóxico dos compostos organoselenados, HSe-01 e HSe-02.

Abstract

Cancer is the second major cause of death in the world and its treatment still requiring the use of therapeutic modalities, physical or drug, although majority of them is effective in terms of removal and attack of cancer cells, especially early in the disease. However, those treatments haven’t been perfectly selective. Consequently, the study of new selective target compounds with therapeutic potential against cancer has been intensified. Selenides compounds are one class of molecules which has shown many biological activities such as antibacterial, antiviral, antifungal and anticancer. In addition, the organoselenium compounds have shown an effect in many kinds of solid tumors including lung and hepatic tumors and also are showed action in lymphoblastic and myeloblastic leukemia. The aim of this study was to analyze the cytotoxic activity of HSe-01 and Hse-02 organoselenium compounds compared to non- cancer and Cell Cancer cells, identifying the type of cell death induced by these molecules. Cell viability was determined by MTT reduction and trypan blue exclusion. The Hse-01 and Hse-02 compounds demonstrated potent cytotoxic effect on human cancer lines (HL-60, K562, K562-Lucena, and Thp-1) and a less expressive cytotoxic effect on non-cancerous cells (HUVEC), from a concentration of 6.25 μM. Due to potent and selectivity cytotoxic effect of the compounds in 24-hour in K562 cells line, it was evaluated the mechanisms of cell death in these cells. The organoselenium compounds showed cell viability reduction in K562 cells with IC50 of 40 μM ± 0.35% and 42.5 μM ± 0.37% for HSe-01 and HSe-02 compounds, respectively. In exclusion test after 24h and incubated at lower concentration (25 μM), the compounds did not reduce the viability in K562 cells. The ability of these compounds to cause molecular changes associated with the type of cell death was evaluated by flow cytometry. After a period of 24h, those compounds did not cause damage to the cell membrane. In concentration of 40 μM, the compound HSe -01 and HSe -02, induced an increase of subdiploid DNA concentration from 9.1±1.9% to 15.6±1.3% and 15.9±1.3%, respectively and arrested in the G1 phase of the cell cycle from 38.6±3.2% to 51.8±3% and 45.4± 4%, respectively and those compounds induced depolarization of mitochondrial membrane from 12.4±4.1% to 28.8± 6.2% and 31.1± 6.8% for HSe-01 and HSe-02, respectively. It was concluded that the HSe-01 and HSe-02 organoselenium compounds showed a potent cytotoxic potential for leukemic cell lines, notably K562 cells, by act possibly by intrinsic apoptosis behaving as potential drug candidates for the study of news molecules against cancer.