title: Telmisartan induces apoptosis and regulates Bcl-2 in human renal cancer cells.
abstract: 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.
authors.affiliation: Post Graduation Program Health Science, Department of Medicine, UFRN, Natal, RN, Cep: 59078-970, Brazil Post Graduation Program in Functional and Structural Biology, Department of Morphology, UFRN, Natal, RN, Cep: 59078-970, Brazil araujojr@cb.ufrn.br.
authors.forename: Raimundo Fernandes
authors.initials: RF
authors.lastname: de Araújo Júnior
authors.affiliation: Post Graduation Program in Pharmaceutical Science, Department of Biophysics and Pharmacology, UFRN, Natal, RN, Cep: 59078-970, Brazil.
authors.forename: Ana Luiza C S
authors.initials: AL
authors.lastname: Leitão Oliveira
authors.affiliation: Biotechnology Laboratory of Natural Polymer-Biopol, Department of Biochemistry, UFRN, Natal, RN, Cep: 59078-970, Brazil.
authors.forename: Raniere Fagundes
authors.initials: RF
authors.lastname: de Melo Silveira
authors.affiliation: Biotechnology Laboratory of Natural Polymer-Biopol, Department of Biochemistry, UFRN, Natal, RN, Cep: 59078-970, Brazil.
authors.forename: Hugo Alexandre
authors.initials: HA
authors.lastname: de Oliveira Rocha
authors.affiliation: The Edmond and Lily Safra International Institute of Neuroscience of Natal (ELS-IINN), Brazil.
authors.forename: Pedro
authors.initials: P
authors.lastname: de França Cavalcanti
authors.affiliation: Post Graduation Program in Public Health/Post Graduation Program in Pharmaceutical Science, Department of Biophysics and Pharmacology, UFRN, Natal, RN, Cep: 59078-970, Brazil.
authors.forename: Aurigena Antunes
authors.initials: AA
authors.lastname: de Araújo
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism*; D017209:Apoptosis; D001562:Benzimidazoles / Q000378:metabolism*; D001565:Benzoates / Q000378:metabolism*; D053148:Caspase 3 / Q000032:analysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*; D000077333:Telmisartan
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; D001565:Benzoates; D019253:Proto-Oncogene Proteins c-bcl-2; D053148:Caspase 3; D000077333:Telmisartan
keywords: Bcl-2; Telmisartan; apoptosis; caspase-3; human cancer cells