tailieunhanh - Báo cáo khoa học: Strong cytotoxic effect of the bradykinin antagonist BKM-570 in ovarian cancer cells – analysis of the molecular mechanisms of its antiproliferative action

The standard chemotherapy for epithelial ovarian cancer (EOC) patients is currently a combination of taxane and platinum. However, most EOC patients still suffer relapses, and there is an immediate need for the devel-opment of novel and more effective therapeutic modalities against this deadly disease. | IFEBS Journal Strong cytotoxic effect of the bradykinin antagonist BKM-570 in ovarian cancer cells - analysis of the molecular mechanisms of its antiproliferative action Stephanie Jutras1 2 Magdalena Bachvarova2 Mamadou Keita1 2 Jean-Loup Bascands3 4 Anne-Marie Mes-Masson5 6 John M. Stewart7 and Dimcho Bachvarov1 2 1 Department of Molecular Medicine LavalUniversity Quebec Canada 2 Cancer Research Centre HopitalL Hotel-Dieu de Quebec Centre Hospitalier Universitaire de Quebec CHUQ Canada 3 Inserm U858 I2MR Department of Cardiac and RenalRemodeling Toulouse France 4 Universite Toulouse III PaulSabatier Institut de Medecine Moleculaire de Rangueil France 5 Department of Medicine Universite de Montreal Canada 6 Centre de Recherche du Centre Hospitalier de l Universite de Montreal CHUM Institut du Cancer de Montreal Canada 7 Department of Biochemistry and Molecular Genetics University of Colorado Health Sciences Center Denver CO USA Keywords BKM-570 bradykinin antagonist bradykinin receptor DNA microarrays ovarian cancer therapy Correspondence D. Bachvarov CHUQ Centre de recherche Hotel-Dieu de Quebec 9 rue McMahon Quebec Quebec Canada G1R 2J6 Fax 1 418 6915439 Tel 1 418 525 4444 ext. 15590 E-mail Received 8 September 2010 revised 9 October 2010 accepted 20 October 2010 doi The standard chemotherapy for epithelial ovarian cancer EOC patients is currently a combination of taxane and platinum. However most EOC patients still suffer relapses and there is an immediate need for the development of novel and more effective therapeutic modalities against this deadly disease. Recently the nonpeptide bradykinin BK antagonist pentafluorocinnamoyl- o-2 6-dichlorobenzyl -l-tyrosine-N- 4-amino- tetramethyl-piperidyl amide BKM-570 was shown to cause impressive growth inhibition of lung and prostate tumors displaying superior in vivo inhibitory effects than convential chemotherapeutic drugs. Here we