Avaliação da citotoxicidade in vitro de derivados indólicos em linhagens tumorais humanas

O câncer é um termo usado para um conjunto de doenças que apresentam alterações na proliferação celular, invasividade e metástase. A quimioterapia é o tratamento mais utilizado na prática clínica da doença e a sua baixa seletividade atinge, também, as células normais. Para aumentar essa seletividade há uma busca por novos compostos. Assim, o indol é um exemplo de produto natural que pode ser encontrado em diversos tipos de sistemas biológicos, como por exemplo, algas, plantas e fungos. Nosso estudo deriva de uma investigação que teve como objetivo avaliar o potencial citotóxico dos derivados indólicos NM–01-24-19 e NM-01-28-22 em três linhagens de células cancerígenas: células de câncer de pulmão (A549), câncer de mama (MCF-7) e câncer de próstata (PC-3). Para alcançar esse objetivo, foi utilizado o procedimento metodológico Sulforrodamina B (SRB). A SRB é um corante aniônico utilizado para quantificação da viabilidade celular após exposição de fármacos. Esse procedimento é relevante, pois apresenta maior precisão quando comparado aos diversos ensaios convencionais de testes farmacológicos de drogas, tal como o MTT. Os resultados obtidos demonstraram que os derivados indólicos NM-01-24-19 e NM-01-28-22 diminuíram o crescimento das linhagens A549, MCF-7 e PC-3. O derivado NM-01-24-19 apresentou atividade citotóxica potente em todas as linhagens de células tumorais humanas, uma vez que apresentou CI50 menor que 10 μM. Entretanto, o derivado do indol NM-01-28-22 demonstrou atividade potente somente na linhagem celular A549, enquanto as demais apresentaram atividade moderada, com CI50 entre 10 - 30 μM. Dessa forma, os derivados indólicos que foram analisados neste estudo são potenciais fármacos com propriedades citotóxicas em células de câncer, sendo necessário novos estudos para elucidar os mecanismos moleculares dos derivados analisados.São Cristóvã

Cytotoxic activity of essential oil from Leaves of Myrcia splendens against A549 Lung Cancer cells

Abstract Background Plants of the Myrcia genus have been widely used in folk medicine to treat various diseases, including cancer. Myrcia splendens species has a diverse chemical constitution, but the biological activities of its essential oil have not been well investigated. In this study to out the chemistry characterization of essential oil (EO) from the leaves of the species M. splendens from Brazil and evaluate cytotoxic effect in A549 lung cancer cells. Methods M. splendens EO was obtained by hydrodistillation and analyzed by Gas Chromatography-Mass Spectrometry (GC-MS). EO was isolated and evaluated for cellular viability in tumor cell lines by MTT assay. The evaluation of the formation of clones and the migratory capacity of the A549 cells treated with EO was done by the clonogenic assay and the wound healing assay. Morphological changes were observed in A549 cells by fluorescence using Phalloidin/FITC and DAPI. Results 22 compounds were identified in the chemical analysis of EO, corresponding to 88% of the sample. Major compounds were the sesquiterpenic hydrocarbons bicyclogermacrene (15.4%), germacrene D (8.9%) and E-caryophyllene (10.1%). The biological analysis of the EO showed high cytotoxic activity with an IC50 below 20 µg/ml in the THP-1, A549 and B16-F10 tumor cells. The treatment with EO reduced colony formation and inhibited the migratory capacity of A549 cells. Furthermore, apoptotic morphological changes in the nucleus and cytoplasm of A549 cells was observed after of treatment with EO. Conclusion The findings of this study suggest that the M. splendens EO has cytotoxic compounds for the A549 lung cancer cells. Treatment with the EO decreased the colony formation and reduced the ability of lung cancer cells to migrate. Future studies may be used to isolate compounds from the EO for the study of lung cancer

Inhibitory effect of O-propargyllawsone in A549 lung adenocarcinoma cells

Abstract Background Lung cancer is the deadliest type of cancer in the world and the search for compounds that can treat this disease is highly important. Lawsone (2-hydroxy-1,4-naphtoquinone) is a naphthoquinone found in plants from the Lawsone genus that show a high cytotoxic effect in cancer cell lines and its derivatives show an even higher cytotoxic effect. Methods Sulforhodamine B was used to evaluate the cytotoxic activity of compounds on tumor cells. Clonogenic assay was used to analyze the reduction of colonies and wound healing assay to the migratory capacity of A549 cells. Apoptosis and necrosis were analyzed by flow cytometer and Giemsa staining. Hemolysis assay to determine toxicity in human erythrocytes. Results Lawsone derivatives were evaluated and compound 1 (O-propargyllawsone) was the one with the highest cytotoxic effect, with IC50 below 2.5 µM in A549 cells. The compound was able to reduce colony formation and inhibit cell migration. Morphological changes and cytometry analysis show that the compound induces apoptosis and necrosis in A549 cells. Conclusions These results show that O-propargyllawsone show a cytotoxic effect and may induce apoptosis in A549 cells