AIMS: Vorinostat (suberoylanilide hydroxamic acid; SAHA) is a histone deacetylase inhibitor (HDACi) approved in the clinics for the treatment of T-cell lymphoma and with the potential to be effective also in breast cancer. We investigated the responsiveness to SAHA in human breast primary tumors and cancer cell lines. RESULTS: We observed a differential response to drug treatment in both human breast primary tumors and cancer cell lines. Gene expression analysis of the breast cancer cell lines revealed that genes involved in cell adhesion and redox pathways, especially glutathione metabolism, were differentially expressed in the cell lines resistant to SAHA compared with the sensitive ones, indicating their possible association with drug resistance mechanisms. Notably, such an association was also observed in breast primary tumors. Indeed, addition of buthionine sulfoximine (BSO), a compound capable of depleting cellular glutathione, significantly enhanced the cytotoxicity of SAHA in both breast cancer cell lines and primary breast tumors. INNOVATION: We identify and validate transcriptional differences in genes involved in redox pathways, which include potential predictive markers of sensitivity to SAHA. CONCLUSION: In breast cancer, it could be relevant to evaluate the expression of antioxidant genes that may favor tumor resistance as a factor to consider for potential clinical application and treatment with epigenetic drugs (HDACis).
AIMS: Vorinostat (suberoylanilide hydroxamic acid; SAHA) is a histone deacetylase inhibitor (HDACi) approved in the clinics for the treatment of T-cell lymphoma and with the potential to be effective also in breast cancer. We investigated the responsiveness to SAHA in humanbreast primary tumors and cancer cell lines. RESULTS: We observed a differential response to drug treatment in both humanbreast primary tumors and cancer cell lines. Gene expression analysis of the breast cancer cell lines revealed that genes involved in cell adhesion and redox pathways, especially glutathione metabolism, were differentially expressed in the cell lines resistant to SAHA compared with the sensitive ones, indicating their possible association with drug resistance mechanisms. Notably, such an association was also observed in breast primary tumors. Indeed, addition of buthionine sulfoximine (BSO), a compound capable of depleting cellular glutathione, significantly enhanced the cytotoxicity of SAHA in both breast cancer cell lines and primary breast tumors. INNOVATION: We identify and validate transcriptional differences in genes involved in redox pathways, which include potential predictive markers of sensitivity to SAHA. CONCLUSION: In breast cancer, it could be relevant to evaluate the expression of antioxidant genes that may favor tumor resistance as a factor to consider for potential clinical application and treatment with epigenetic drugs (HDACis).
Authors: Vered Stearns; Lisa K Jacobs; Maryjo Fackler; Theodore N Tsangaris; Michelle A Rudek; Michaela Higgins; Julie Lange; Zandra Cheng; Shannon A Slater; Stacie C Jeter; Penny Powers; Susanne Briest; Calvin Chao; Carl Yoshizawa; Elizabeth Sugar; Igor Espinoza-Delgado; Saraswati Sukumar; Edward Gabrielson; Nancy E Davidson Journal: Clin Cancer Res Date: 2013-05-29 Impact factor: 12.531
Authors: P J O'Dwyer; T C Hamilton; F P LaCreta; J M Gallo; D Kilpatrick; T Halbherr; J Brennan; M A Bookman; J Hoffman; R C Young; R L Comis; R F Ozols Journal: J Clin Oncol Date: 1996-01 Impact factor: 44.544
Authors: Nívea Dias Amoêdo; Mariana Figueiredo Rodrigues; Paula Pezzuto; Antonio Galina; Rodrigo Madeiro da Costa; Fábio Ceneviva Lacerda de Almeida; Tatiana El-Bacha; Franklin David Rumjanek Journal: PLoS One Date: 2011-07-18 Impact factor: 3.240
Authors: W Weichert; A Röske; V Gekeler; T Beckers; C Stephan; K Jung; F R Fritzsche; S Niesporek; C Denkert; M Dietel; G Kristiansen Journal: Br J Cancer Date: 2008-01-22 Impact factor: 7.640