Ursolic acid triggers apoptosis and Bcl-2 downregulation in MCF-7 breast cancer cells.
In this report we determine the ability of ursolic acid (UA) to induce apoptosis and to modulate glucocorticoid receptor (GR) and Activator Protein-1 (AP-1) in MCF-7 cells. The UA-induced apoptosis (53 microM), the PARP cleavage, and the decrease in Bcl-2 protein (53 microM) support the notion that UA induces apoptosis through the intrinsic mitochondrial pathway. UA binds GR (relative binding affinity: 2.57) and translocates GR into nucleus, suggesting its potential as a GR modulator. UA had no effect on GRE- or TRE-driven gene expression. In summary, UA is a GR modulator and may be considered as a potential anticancer agent in breast cancer.
Kassi
E
E
Laboratory of Biological Chemistry, Medical School, University of Athens, Athens, Greece.
Sourlingas
T G
TG
Spiliotaki
M
M
Papoutsi
Z
Z
Pratsinis
H
H
Aligiannis
N
N
Moutsatsou
P
P
D021581:Active Transport, Cell Nucleus; D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019254:Genes, bcl-2; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014221:Triamcinolone / Q000494:pharmacology; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
D000970:Antineoplastic Agents; D003907:Dexamethasone; D015735:Mifepristone; D009363:Neoplasm Proteins; D011065:Poly(ADP-ribose) Polymerases; D019253:Proto-Oncogene Proteins c-bcl-2; D011965:Receptors, Glucocorticoid; D018808:Transcription Factor AP-1; D014221:Triamcinolone; D014315:Triterpenes; D000097245:Ursolic Acid