AIM: To study in vitro the molecular mechanism of apoptosis caused by beta-lapachone, a quinone obtained from the bark of the lapacho tree (Tabebuia avellanedae). MATERIALS AND METHODS: The study was carried out on human bladder carcinoma T24 cell line. Determination of cell viability was done using trypan blue exclusion method, apoptosis quantitative estimation - by DAPI staining and agarose gel electrophoresis for DNA fragmentation. Flow cytometry analysis, RT-PCR and Western blot analysis, colorimetric assay of caspase activity were applied as well. RESULTS: It was found that in micromolar range of concentrations beta-lapachone inhibited the viability of T24 cells by inducing apoptosis, which could be proved by formation of apoptotic bodies and DNA fragmentation. Treatment of T24 cells with beta-lapachone resulted in a down-regulation of Bcl-2 expression and up-regulation of Bax expression. beta-lapachone-induced apoptosis was also associated with activation of caspase-3 and caspase-9, inhibition of IAP expression, and degradation of poly (ADP-ribose) polymerase, phospholipase C-gamma1 and beta-catenin proteins. At the same time Fas and FasL levels were inhibited upon treatment with beta-lapachone in a concentration-dependent manner. CONCLUSION: beta-lapachone-induced apoptosis in T24 cells is mediated, at least in part, by the mitochondrial-signaling pathway.
AIM: To study in vitro the molecular mechanism of apoptosis caused by beta-lapachone, a quinone obtained from the bark of the lapacho tree (Tabebuia avellanedae). MATERIALS AND METHODS: The study was carried out on human bladder carcinoma T24 cell line. Determination of cell viability was done using trypan blue exclusion method, apoptosis quantitative estimation - by DAPI staining and agarose gel electrophoresis for DNA fragmentation. Flow cytometry analysis, RT-PCR and Western blot analysis, colorimetric assay of caspase activity were applied as well. RESULTS: It was found that in micromolar range of concentrations beta-lapachone inhibited the viability of T24 cells by inducing apoptosis, which could be proved by formation of apoptotic bodies and DNA fragmentation. Treatment of T24 cells with beta-lapachone resulted in a down-regulation of Bcl-2 expression and up-regulation of Bax expression. beta-lapachone-induced apoptosis was also associated with activation of caspase-3 and caspase-9, inhibition of IAP expression, and degradation of poly (ADP-ribose) polymerase, phospholipase C-gamma1 and beta-catenin proteins. At the same time Fas and FasL levels were inhibited upon treatment with beta-lapachone in a concentration-dependent manner. CONCLUSION: beta-lapachone-induced apoptosis in T24 cells is mediated, at least in part, by the mitochondrial-signaling pathway.
Authors: Renata G Almeida; Wagner O Valença; Luísa G Rosa; Carlos A de Simone; Solange L de Castro; Juliana M C Barbosa; Daniel P Pinheiro; Carlos R K Paier; Guilherme G C de Carvalho; Claudia Pessoa; Marilia O F Goulart; Ammar Kharma; Eufrânio N da Silva Júnior Journal: RSC Med Chem Date: 2020-07-13
Authors: Guilherme A M Jardim; Daisy J B Lima; Wagner O Valença; Daisy J B Lima; Bruno C Cavalcanti; Claudia Pessoa; Jamal Rafique; Antonio L Braga; Claus Jacob; Eufrânio N da Silva Júnior; Eduardo H G da Cruz Journal: Molecules Date: 2017-12-30 Impact factor: 4.411
Authors: Chun-Liang Chen; Ling Cen; Jennifer Kohout; Brian Hutzen; Christina Chan; Fu-Chuan Hsieh; Abbey Loy; Victor Huang; Gong Cheng; Jiayuh Lin Journal: Mol Cancer Date: 2008-10-21 Impact factor: 27.401
Authors: Tânia C S P Pires; Maria Inês Dias; Ricardo C Calhelha; Ana Maria Carvalho; Maria-João R P Queiroz; Lillian Barros; Isabel C F R Ferreira Journal: Molecules Date: 2015-12-21 Impact factor: 4.411
Authors: Agata Kowalczyk; Artur Kasprzak; Magdalena Poplawska; Monika Ruzycka; Ireneusz P Grudzinski; Anna M Nowicka Journal: Int J Mol Sci Date: 2020-08-14 Impact factor: 6.208
Authors: Matthew J Foulkes; Faith H Tolliday; Katherine M Henry; Stephen A Renshaw; Simon Jones Journal: PLoS One Date: 2020-10-06 Impact factor: 3.240