RESUMO
AIMS: Oncology treatments aim at selective toxicity for tumor (compared to normal) cells, and chromone- coumarin hybrids have shown such activity. METHODS: In this study, we test a novel series of synthetic chromone and coumarin derivatives (1-9) for cytotoxic activity against a panel of tumor cell lines (MCF-7, A549, HepG2, HTC-116, B16 and Caco-2) opposed to non-tumor cells (HEK-293t). Electrical impedance spectroscopy was used to monitor cell viability in real time. RESULTS: Compound 8 showed the most potent activity, and it significantly diminished cancer cell proliferation and viability in different cell lines. It induced apoptosis in a dose-dependent manner, as shown by Western blot and flow cytometry. CONCLUSION: Electrical impedance spectroscopy appears to be a convenient tool for in vitro cytotoxicity analysis, which could be useful for identifying drug effects and side effects during early phases of drug discovery and development.
Assuntos
Antineoplásicos/farmacologia , Cromonas/farmacologia , Cumarínicos/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromonas/química , Cumarínicos/química , Espectroscopia Dielétrica , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Impedância Elétrica , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
BACKGROUND/AIM: NF-ĸB affects most aspects of cellular physiology. Deregulation of NF-ĸB signaling is associated with inflammatory diseases and cancer. In this study, we evaluated the cytotoxic and NF-ĸB inhibition potential of new spiro(lactone-cyclohexanone) compounds in two different human leukemia cell lines (U937 and K562). MATERIALS AND METHODS: The anti-proliferative effects of the spiro(lactone-cyclohexanone) compounds on human K562 and U937 cell lines was evaluated by trypan blue staining, as well as their involvement in NF-kB regulation were analyzed by luciferase reporter gene assay, Caspase-3/7 activities were evaluated to analyze apoptosis induction. RESULTS: Both spiro(coumarin-cyclohexanone) 4 and spiro(6- methyllactone-cyclohexanone) 9 down-regulated cancer cell viability and proliferation. Compound 4 inhibited TNF-α-induced NF-ĸB activation in a dose-dependent manner and induced caspase-dependent apoptosis in both leukemia cell lines. CONCLUSION: Results show that compound 4 and compound 9 have potential as anti-cancer agents. In addition, compound 4 exerted NF-kB inhibition activity in leukemia cancer cells.
