It has been well-characterized that the renin-angiotensin system (RAS) physiologically regulates systemic arterial pressure. However, RAS signaling has also been shown to increase cell proliferation during malignancy, and angiotensin receptor blockers (ARBs) are able to decrease pro-survival signaling by inhibiting anti-apoptotic molecules and suppressing caspase activity. In this study, the apoptotic effects of telmisartan, a type of ARB, was evaluated using a non-cancerous human renal cell line (HEK) and a human renal cell carcinoma (RCC) cell line (786). Both types of cells were treated with telmisartan for 4 h, 24 h, and 48 h, and then were assayed for levels of apoptosis, caspase-3, and Bcl-2 using MTT assays, flow cytometry, and immunostaining studies. Analysis of variance was used to identify significant differences between these data (P < 0.05). Following the treatment of 786 cells with 100 µM and 200 µM telmisartan, a marked inhibition of cell proliferation was observed. 50 µM cisplatin also caused high inhibition of these cells. Moreover, these inhibitions were both concentration- and time-dependent (P < 0.05). Various apoptotic effects were also observed compared with control cells at the 24 h and 48 h timepoints assayed (P < 0.001). Furthermore, positive caspase-3 staining and down-regulation of Bcl-2 were detected, consistent with induction of cell death. In contrast, treatment of HEK cells with telmisartan did not produce an apoptotic effect compared with control cells at the 24 h timepoint (P > 0.05). Treatment with cisplatin promoted in HEK cells high index of apoptosis (P < 0.001). Taken together, these results suggest that telmisartan induces apoptosis via down-regulation of Bcl-2 and involvement of caspase-3 in human RCC cells.

<div>Células-tronco mesenquimais apresentam excelentes características para o uso em terapia celular. Contudo, os protocolos</div><div>de extração, manutenção e expansão dessas células ainda necessitam de uma padronização. A proposta do nosso trabalho</div><div>foi avaliar a influência do período de pré-cultivo (PPC), tempo de tripsinização (TT) e adição de meio condicionado (IMC) com</div><div>relação ao rendimento de uma cultura primária de células-tronco mesenquimais extraídas da medula óssea de</div><div>camundongos. Nossos resultados mostram que os grupos de células cultivadas em PPC de 72 horas mostraram um melhor</div><div>rendimento celular, quando comparadas às de PPC de 24 horas. O TT não apresentou diferença significativa entre 5 e 10</div><div>minutos, embora a viabilidade celular se mantivesse acima de 90% para os dois tempos avaliados. O meio condicionado</div><div>adicionado à cultura primária parece não influenciar significativamente o rendimento celular. Concluímos que o uso de um</div><div>PPC de 72 horas aumenta significativamente o número de células obtidas em cultura primária de medula óssea.</div>