TY - JOUR
T1 - Redox-Mediated Suberoylanilide Hydroxamic Acid Sensitivity in Breast Cancer
AU - Chiaradonna, Ferdinando
AU - Barozzi, Iros
AU - Miccolo, Claudia
AU - Bucci, Gabriele
AU - Palorini, Roberta
AU - Fornasari, Lorenzo
AU - Botrugno, Oronza A.
AU - Pruneri, Giancarlo
AU - Masullo, Michele
AU - Passafaro, Alfonso
AU - Galimberti, Viviana E.
AU - Fantin, Valeria R.
AU - Richon, Victoria M.
AU - Pece, Salvatore
AU - Viale, Giuseppe
AU - Di Fiore, Pier Paolo
AU - Draetta, Giulio
AU - Pelicci, Pier Giuseppe
AU - Minucci, Saverio
AU - Chiocca, Susanna
N1 - Publisher Copyright:
© Copyright 2015, Mary Ann Liebert, Inc. 2015.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - 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).
AB - 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).
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U2 - 10.1089/ars.2014.6189
DO - 10.1089/ars.2014.6189
M3 - Article
C2 - 25897982
AN - SCOPUS:84934894856
SN - 1523-0864
VL - 23
SP - 15
EP - 29
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
IS - 1
ER -