RESUMO
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.
Assuntos
2,2'-Dipiridil/análogos & derivados , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Citotoxinas/farmacologia , Níquel/farmacologia , Compostos Organometálicos/farmacologia , Compostos Organoplatínicos/farmacologia , Platina/farmacologia , 2,2'-Dipiridil/química , 2,2'-Dipiridil/farmacologia , 2,2'-Dipiridil/toxicidade , Antineoplásicos/síntese química , Antineoplásicos/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Complexos de Coordenação/química , Complexos de Coordenação/toxicidade , Citotoxinas/síntese química , Citotoxinas/química , Citotoxinas/toxicidade , Relação Dose-Resposta a Droga , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Modelos Moleculares , Estrutura Molecular , Níquel/química , Níquel/toxicidade , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Compostos Organoplatínicos/química , Compostos Organoplatínicos/toxicidade , Platina/química , Platina/toxicidade , Relação Estrutura-Atividade , Telomerase/antagonistas & inibidores , Telomerase/metabolismoRESUMO
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.
Assuntos
DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Dípteros/genética , Evolução Molecular , Filogenia , Algoritmos , Animais , Sequência de Bases , Teorema de Bayes , Sequência Conservada , Dípteros/classificação , Especiação Genética , Sequências Repetitivas Dispersas/genética , Modelos Moleculares , Dados de Sequência Molecular , Polimorfismo Genético , Alinhamento de Sequência , Sequências de Repetição em Tandem/genéticaRESUMO
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.
