RESUMEN
Two metal complexes of NiLCl2 (1) and [PtLCl]Cl (2) with 4-([2,2':6',2â³-terpyridin]-4'-yl)-N,N-diethylaniline (L) were synthesized and characterized. 1 and 2 exhibited selective cytotoxicity to T-24 cells more than L, compared with the normal liver cell line (HL-7702). Various experiments showed that L, 1 and 2 caused T-24 cell cycle arrest at S phase, as shown by the down-regulation of cdc25 A, cyclin A, cyclin B and CDK2 and the up-regulation of p21, p27 and p53. Furthermore, complexes 1 and 2, especially complex 2, acted as telomerase inhibitors targeting c-myc G-quadruplex DNA and triggered cell apoptosis. In addition, 1 and 2 also caused mitochondrial dysfunction. Taken together, we found that 1 and 2 exerted their cytotoxic activity mainly via inhibiting telomerase by interaction with c-myc quadruplex and disruption of mitochondrial function.
Asunto(s)
2,2'-Dipiridil/análogos & derivados , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Complejos de Coordinación/farmacología , Citotoxinas/farmacología , Níquel/farmacología , Compuestos Organometálicos/farmacología , Compuestos Organoplatinos/farmacología , Platino (Metal)/farmacología , 2,2'-Dipiridil/química , 2,2'-Dipiridil/farmacología , 2,2'-Dipiridil/toxicidad , Antineoplásicos/síntesis química , Antineoplásicos/química , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Complejos de Coordinación/química , Complejos de Coordinación/toxicidad , Citotoxinas/síntesis química , Citotoxinas/química , Citotoxinas/toxicidad , Relación Dosis-Respuesta a Droga , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Modelos Moleculares , Estructura Molecular , Níquel/química , Níquel/toxicidad , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Compuestos Organoplatinos/química , Compuestos Organoplatinos/toxicidad , Platino (Metal)/química , Platino (Metal)/toxicidad , Relación Estructura-Actividad , Telomerasa/antagonistas & inhibidores , Telomerasa/metabolismoRESUMEN
The resolution potential of internal transcribed spacer 2 (ITS2) at deeper levels remains controversial. In this study, 105 ITS2 sequences of 55 species in Calyptratae were analyzed to examine the phylogenetic utility of the spacer above the subfamily level and to further understand its evolutionary characteristics. We predicted the secondary structure of each sequence using the minimum-energy algorithm and constructed two data matrixes for phylogenetic analysis. The ITS2 regions of Calyptratae display strong A-T bias and slight variation in length. The tandem and dispersed repeats embedded in the spacers possibly resulted from replication slippage or transposition. Most foldings conformed to the four-domain model. Sequence comparison in combination with the secondary structures revealed six conserved motifs. Covariation analysis from the conserved motifs indicated that the secondary structure restrains the sequence evolution of the spacer. The deep-level phylogeny derived from the ITS2 data largely agreed with the phylogenetic hypotheses from morphologic and other molecular evidence. Our analyses suggest that the accordant resolutions generated from different analyses can be used to infer deep-level phylogenetic relations.
Asunto(s)
ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Dípteros/genética , Evolución Molecular , Filogenia , Algoritmos , Animales , Secuencia de Bases , Teorema de Bayes , Secuencia Conservada , Dípteros/clasificación , Especiación Genética , Secuencias Repetitivas Esparcidas/genética , Modelos Moleculares , Datos de Secuencia Molecular , Polimorfismo Genético , Alineación de Secuencia , Secuencias Repetidas en Tándem/genéticaRESUMEN
AIM: To investigate the effect of Tripterygium hypoglaucum Hutch (THH) on the assembly and disassembly process of tubulin and its possible mode of action. METHODS: In vitro porcine brain tubulin assembly assay was employed to analyze the inhibitory effects of THH at different concentrations (0.05 microg/L, 0.07 microg/L, 0.09 microg/L). Colchicine (0.0025 mmol/L, 0.0050 mmol/L, 0.0075 mmol/L) was used as a positive control. RESULTS: THH could significantly inhibit the assembly of isolated porcine brain tubulin at all tested concentrations. CONCLUSION: THH is capable of inducing aneuploidy in mammals via tubulin polymerization inhibition pathway and may pose a genetic risk to human beings.
