RESUMEN
Ideal drugs to cure cancer leave normal cells unharmed while selectively turning tumor cells unviable. Several copper complexes have been able to selectively slow down tumor proliferation. We hypothesized that Cu(smz)2(bipy)·H2O (1)-a copper-complex that has two ligands capable of interacting with DNA-would outperform Cu(smz)2(OH2)·2H2O (2), and also that supporting 1 on mesoporous silica spheres would decrease even further tumor cell viability in vitro. After exposing osteosarcoma cells (MG-63) and normal phenotype cells of bone origin (MC3T3-E1) to either complex, we studied their toxic effect and mechanisms of action. We determined cell viability (MTT assay) and quantified formation of reactive oxygen species (oxidation of DHR-123 to rhodamine). Moreover, we assessed genotoxicity from (i) formation of micronucleus (MN assay) and (ii) damage of DNA (Comet assay). After the exposure of 1 supported on silica spheres, we tested cell viability. Our results confirm our hypotheses: inhibition of tumor cells follows: supported 1 > dissolved 1 > 2. Future work that enhances the load of the complex exclusively in mesopores may improve the ability of 1 to further inhibit tumor cell viability.
Asunto(s)
2,2'-Dipiridil/farmacología , Antineoplásicos/farmacología , Complejos de Coordinación/farmacología , Cobre/farmacología , Microesferas , Osteosarcoma/genética , Osteosarcoma/patología , Sulfametazina/farmacología , 2,2'-Dipiridil/química , Células 3T3 , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Cobre/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ratones , Estructura Molecular , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/metabolismo , Tamaño de la Partícula , Porosidad , Especies Reactivas de Oxígeno/análisis , Especies Reactivas de Oxígeno/metabolismo , Dióxido de Silicio/química , Relación Estructura-Actividad , Sulfametazina/química , Propiedades de SuperficieRESUMEN
Cancer is a group of diseases involving abnormal cell growth. The cells grow uncontrollably with the potential to invade and spread to other parts of the body. This disease is one of the principal death causes in the world, thus becoming a significant topic of scientific research. On the other hand, transition metals play a fundamental role in different living systems. In particular, Metallodrugs represent new and powerful tools for diverse therapeutic applications. To date, various metallodrugs display interesting biological activities for chemotherapy. In this field, cisplatin was the first inorganic compound with high relevance in cancer treatment. This compound was a leader agent in clinical use. Toxicity and resistance problems trigger the development of other platinum drugs with better clinical perspective and also raise the scientific interest for the putative antitumor properties of V, Ru and Cu compounds. Several scientific articles show that complexes of these metals are the new metal-based drugs used in the treatment of several cancers, such us, lung, colon, breast, bladder, etc. In this review we recapitulate current information and new advances on antitumor in vitro effects of several organic and inorganic compounds derived from copper, ruthenium and vanadium. These metal derived compounds targeting DNA or cell proteins involved in cell signaling pathways related to cancer. The mechanisms of cell death of these metallodrugs have also been comprehensibly reviewed. The knowledge of these mechanisms of death and the relationship between chemical structure and biological activity may be useful for the design of new metal-based drugs with promising pharmacologic applications as anticancer agents.