Valproic acid is a selective antiproliferative agent in estrogen-sensitive breast cancer cells.
Treatment efficacy of breast cancer can be impaired by cell resistance. The aim of the study was to investigate the anti-tumour effects of valproic acid (VPA), the only clinically available histone deacetylase inhibitor, on both estrogen-sensitive and -insensitive breast cancer cells. VPA, at a concentration lacking severe adverse effects in human, reduces cell viability in estrogen-sensitive cell lines, inducing p21 expression and impairing cell cycle. In ZR-75-1, cell cycle is selectively arrested in G1, whereas MCF-7 cells massively accumulated in sub-G1. Actually, in MCF-7 cells, VPA induces apoptosis, down-regulates Bcl-2 and up-regulates Bak expression. In conclusion, VPA is a powerful antiproliferative agent in estrogen-sensitive breast cancer cells, making this drug of clinical interest as a new approach to treat breast cancer.
Fortunati
Nicoletta
N
Oncological Endocrinology, ASO San Giovanni Battista, Via Genova 3, 10126 Turin, Italy.
Bertino
Silvia
S
Costantino
Lucia
L
Bosco
Ornella
O
Vercellinatto
Ilenia
I
Catalano
Maria Graziella
MG
Boccuzzi
Giuseppe
G
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; C494772:BAK1 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004791:Enzyme Inhibitors; D004967:Estrogens; D056572:Histone Deacetylase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D050998:bcl-2 Homologous Antagonist-Killer Protein; D014635:Valproic Acid; C505530:CASP8 protein, human; D053181:Caspase 8; D053453:Caspase 9; D006655:Histone Deacetylases