Histone deacetylase inhibitor FR235222 sensitizes human prostate adenocarcinoma cells to apoptosis through up-regulation of Annexin A1.
The reduction of Annexin A1 (ANXA1) expression, commonly associated with prostate cancer, could be due to elevated activity of histone deacetylases. We have investigated the mechanisms of apoptotic effects of FR235222 in LNCaP cell line and the role of ANXA1. We showed that treatment with FR235222 induced apoptosis through a caspase-dependent mechanism. FR235222 was able to increase the protein levels of ANXA1 at a transcriptional level. Finally, the inhibition of ANXA1 expression by siRNA leads to a partial reduction of FR235222-induced apoptosis. The results suggest that elevated activity of HDACs is responsible for the reduction of ANXA1, indicating that ANXA1 expression is a contributing factor to the proapoptotic effects in prostate cancer.
Dipartimento di Scienze Farmaceutiche, Università di Salerno, Fisciano, Salerno, Italy.
Cosimo Walter
CW
D'Acunto
Bianca
B
Fontanella
Manuela
M
Rodriquez
Maurizio
M
Taddei
Luca
L
Parente
Antonello
A
Petrella
D000107:Acetylation; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation
D017305:Annexin A1; C474179:FR 235222; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D010456:Peptides, Cyclic; D034741:RNA, Small Interfering; D053148:Caspase 3; D006655:Histone Deacetylases