RESUMO
BACKGROUND: Alpha-terpineol is monoterpene alcohol with anti-tumor activity against different tumor cell lines (lung, breast, leukemias and colorectal) through blockage of NF-kB expression, which play an important role in tumor cells growth. OBJECTIVE: Evaluate the antitumor activity of alpha-terpineol in murine Sarcoma 180 cell line. METHODS: For the tests, different cytotoxic and genotoxic assays were used, including Trypan blue, cytokinesis- blocked micronucleus assay, comet assay, agarose gel DNA fragmentation, flow cytometry and cell viability using fluorescence. Ascitic fluid cells from sarcoma 180 were obtained from Mus musculus peritoneal cavity and Alpha-terpineol was tested at 100, 250 and 500 µg/mL. Doxorubicin and Cisplatin were used as positive controls. RESULTS: Cytotoxic effects of alpha-terpineol were found in all concentrations tested, reducing cell viability in 50.9; 38.53; 30.82% at 100, 250 and 500 µg/mL, respectively. Alpha-terpineol induced genotoxic effects due to DNA fragmentation (increased frequency and index of damage), and was clastogenic by increased micronuclei formation, nucleoplasmic bridges and nuclear buds. DNA fragmentation and increased cell death indicated that alpha-terpineol can cause early, late, and necrotic apoptosis. CONCLUSION: Our data indicate that alpha-terpineol has antitumor activity revealed by cytogenetic mechanisms and / or loss of cell membrane integrity.
Assuntos
Antineoplásicos/farmacologia , Monoterpenos Cicloexânicos/farmacologia , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , HumanosRESUMO
BACKGROUND: The search for novel metallic chemical compounds with toxicogenic effects has been of great importance for more efficient cancer treatment. OBJECTIVE: The study evaluated the cytotoxic, genotoxic and mutagenic activity of organoteluran RF07 in the S-180 cell line. METHODS: The bioassays used were cell viability with 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test, evaluation of apoptosis and necrosis using fluorescence and flow cytometry, cytokinesisblock micronucleus test and comet assay. The compound was tested at 1; 2.5 and 5µM. RESULTS: The results showed the cytotoxicity of RF07 at concentrations of 2.5, 5, 10 and 20µM when compared to the negative control. For genotoxicity tests, RF07 showed effects in all concentrations assessed by increased index and frequencies of damage and mutagenic alterations. The compound was also cytotoxic due to the significant decrease in the nuclear division index, with significant values of apoptosis and necrosis. The results of fluorescence and flow cytometry showed apoptosis as the main type of cell death caused by RF07 at 5µM, which is thought to avoid an aggressive immune response of the organism. CONCLUSION: In addition to cytotoxic and genotoxic effects, RF07 creates good perspectives for future antitumor formulations.