RESUMEN
Cisplatin remains one of the most effective current chemotherapeutic agents; however, metal complexes synthesis has increased in order to produce new anti-neoplastic drugs with DNA binding and apoptotic activities in tumor cells and less toxicity for patients. In this study, we evaluated the cytotoxic activity of a novel copper(II) complex (LQM402) against cervical cancer cell lines and found that LQM402 exhibited selective cytotoxicity against HeLa and Ca Ski cells. FITC-annexin assay and DNA fragmentation indicated that apoptosis could be involved in HeLa cell death. Caspase 3/7 and cytochrome c analysis by immunoblotting suggest the intrinsic pathway. LQM402 is a lipid peroxidation inductor according to TBARS production. Additionally, the Ames and micronucleus tests demonstrated non-genotoxic activity for this compound in Salmonella typhimurium and CD1 mice, respectively. Therefore, LQM402 may be a promising and safe anti-cervical cancer compound.
Asunto(s)
Apoptosis/efectos de los fármacos , Complejos de Coordinación/farmacología , Cobre/química , Mutágenos/toxicidad , Oxidantes/metabolismo , Neoplasias del Cuello Uterino/tratamiento farmacológico , Animales , Anexinas , Química Encefálica/efectos de los fármacos , Caspasa 3/metabolismo , Caspasa 7/metabolismo , Línea Celular Tumoral , Colorantes , Complejos de Coordinación/toxicidad , Citocromos c/metabolismo , Citosol/metabolismo , Fragmentación del ADN/efectos de los fármacos , Femenino , Citometría de Flujo , Fluoresceína-5-Isotiocianato , Células HeLa , Humanos , Etiquetado Corte-Fin in Situ , Peroxidación de Lípido/efectos de los fármacos , Ratones , Pruebas de Micronúcleos , Pruebas de Mutagenicidad , Fosfatidilserinas/metabolismo , Ratas , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/metabolismo , Sales de Tetrazolio , Tiazoles , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patologíaRESUMEN
BACKGROUND: Among NSAIDs acetyl salicylic acid remains as a valuable tool because of the variety of benefic prophylactic and therapeutic effects. Nevertheless, the molecular bases for these responses have not been complete understood. We explored the effect of acetyl salicylic acid on the heat shock response. RESULTS: Peripheral blood mononuclear cells from rats challenged with acetyl salicylic acid presented a faster kinetics of expression of HSP-72 messenger RNA and protein in response to in vitro heat shock. This effect reaches its maximum 2 h after treatment and disappeared after 5 h. On isolated peripheral blood mononuclear cells from untreated rats, incubation with acetyl salicylic acid was ineffective to produce priming, but this effect was mimicked when the cells were incubated with the combination of H2O2+ ASA. CONCLUSIONS: Administration of acetyl salicylic acid to rats alters HSP-72 expression mechanism in a way that it becomes more efficient in response to in vitro heat shock. The fact that in vitro acetyl salicylic acid alone did not induce this priming effect implies that in vivo other signals are required. Priming could be reproduces in vitro with the combination of acetyl salicylic acid+H2O2.