RESUMO
Heptaphylline derivatives are carbazoles in Clausena harmandiana, a medicinal plant that is utilized for headache, stomach ache, and other treatments of illness. The present study examined the effects of heptaphylline and 7-methoxyheptaphylline on apoptosis of human colon adenocarcinoma cells (HT-29 cell line). Quantification of cell viability was performed using cell proliferation assay (MTT assay) and of protein expression through immunoblotting. The results showed that only heptaphylline, but not 7-methoxyheptaphylline, significantly significantly activated cleaved of caspase-3 and poly (ADP-ribose) polymerase (PARP-1) which resulted in HT-29 cell death. We found that heptaphylline activated BH3 interacting-domain death agonist (Bid) and Bak, proapoptotic proteins. In contrast, it suppressed X-linked inhibitor-of-apoptosis protein (XIAP), Bcl-xL and survivin, inhibitors of apoptosis. In addition, heptaphylline inhibited activation of NF-κB/p65 (rel), a regulator of apoptotic regulating proteins by suppressing the activation of Akt and IKKα, upstream regulators of p65. The findings suggested that heptaphylline induces apoptosis in human colon adenocarcinoma cells .
Assuntos
Adenocarcinoma/metabolismo , Apoptose/efeitos dos fármacos , Carbazóis/farmacologia , Neoplasias do Colo/metabolismo , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Fator de Transcrição RelA/efeitos dos fármacos , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/efeitos dos fármacos , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/metabolismo , Caspase 3/efeitos dos fármacos , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células HT29 , Humanos , Quinase I-kappa B/efeitos dos fármacos , Quinase I-kappa B/metabolismo , Proteínas Inibidoras de Apoptose/efeitos dos fármacos , Proteínas Inibidoras de Apoptose/metabolismo , Poli(ADP-Ribose) Polimerase-1 , Poli(ADP-Ribose) Polimerases/efeitos dos fármacos , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Survivina , Fator de Transcrição RelA/metabolismo , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/efeitos dos fármacos , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Proteína Killer-Antagonista Homóloga a bcl-2/efeitos dos fármacos , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Proteína bcl-X/efeitos dos fármacos , Proteína bcl-X/metabolismoRESUMO
Protein-protein interactions have a key role in transduction pathways that regulate many cellular functions. Structural and functional properties of protein-protein interface are now better understood, therefore offering attractive opportunities for therapeutic intervention. Developping small molecules that modulate protein-protein interactions is challenging. Nethertheless, significant progress in this endeavour has been made on several fronts. Here, we use few illustrative examples to summarize recent work in this emerging field.