PARP inhibitor ABT-888 affects response of MDA-MB-231 cells to doxorubicin treatment, targeting Snail expression.
To overcome cancer cells resistance to pharmacological therapy, the development of new therapeutic approaches becomes urgent. For this purpose, the use of poly(ADP-ribose) polymerase (PARP) inhibitors in combination with other cytotoxic agents could represent an efficacious strategy. Poly(ADP-ribosyl)ation (PARylation) is a post-translational modification that plays a well characterized role in the cellular decisions of life and death. Recent findings indicate that PARP-1 may control the expression of Snail, the master gene of epithelial-mesenchymal transition (EMT). Snail is highly represented in different resistant tumors, functioning as a factor regulating anti-apoptotic programmes. MDA-MB-231 is a Snail-expressing metastatic breast cancer cell line, which exhibits chemoresistance properties when treated with damaging agents. In this study, we show that the PARP inhibitor ABT-888 was capable to modulate the MDA-MB-231 cell response to doxorubicin, leading to an increase in the rate of apoptosis. Our further results indicate that PARP-1 controlled Snail expression at transcriptional level in cells exposed to doxorubicin. Given the increasing interest in the employment of PARP inhibitors as chemotherapeutic adjuvants, our in vitro results suggest that one of the mechanisms through which PARP inhibition can chemosensitize cancer cells in vivo, is targeting Snail expression thus promoting apoptosis.
Department of Cellular Biotechnologies and Haematology, "Sapienza" University of Rome, Italy.
Germano
G
Mariano
Department of Cellular Biotechnologies and Haematology, "Sapienza" University of Rome, Italy.
Maria Rosaria
MR
Ricciardi
Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, Rome, Italy.
Daniela
D
Trisciuoglio
Department of Cellular Biotechnologies and Haematology, "Sapienza" University of Rome, Italy.|Pasteur Institute-Fondazione Cenci Bolognetti, Rome, Italy.
Michele
M
Zampieri
Department of Cellular Biotechnologies and Haematology, "Sapienza" University of Rome, Italy.|Pasteur Institute-Fondazione Cenci Bolognetti, Rome, Italy.
Fabio
F
Ciccarone
Department of Cellular Biotechnologies and Haematology, "Sapienza" University of Rome, Italy.|Pasteur Institute-Fondazione Cenci Bolognetti, Rome, Italy.
Tiziana
T
Guastafierro
Department of Cellular Biotechnologies and Haematology, "Sapienza" University of Rome, Italy.|Pasteur Institute-Fondazione Cenci Bolognetti, Rome, Italy.
Roberta
R
Calabrese
Department of Cellular Biotechnologies and Haematology, "Sapienza" University of Rome, Italy.
Elisabetta
E
Valentini
Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Italy.
Agostino
A
Tafuri
Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, Rome, Italy.
Donatella
D
Del Bufalo
Department of Cellular Biotechnologies and Haematology, "Sapienza" University of Rome, Italy.|Pasteur Institute-Fondazione Cenci Bolognetti, Rome, Italy.
Paola
P
Caiafa
Department of Cellular Biotechnologies and Haematology, "Sapienza" University of Rome, Italy.
Anna
A
Reale
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001562:Benzimidazoles / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics; D061986:MCF-7 Cells; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D001562:Benzimidazoles; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C521013:veliparib; D004317:Doxorubicin; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases
PARP inhibitors; Snail; breast cancer; chemoresistance