Estrogen in combination with 5-azacitidine up-regulates p75NTR expression and induces apoptosis in 22Rv1 prostate cancer cells.

Previous studies suggest that the low-affinity neurotrophin receptor p75NTR inhibits the proliferation of human prostate cancer cells, and that estrogen interacts with p75NTR in many tissues. In this study, we exposed 22Rv1 androgen-independent prostate cancer cells to 17-β-estradiol and the DNA demethylating agent 5-azacitidine (5-AzaC) to explore the interactions between estrogen and p75NTR. We found that estrogen induced estrogen receptor (ESR) subtype?2 and p75NTR expression in 22Rv1 cells, and that 5-AzaC further enhanced these effects. Estrogen in combination with 5-AzaC induced cell apoptosis, which was associated with the inhibition of NF-κB translocation to the nucleus. These results provide evidence that the up-regulation of ESR2 and p75NTR by estrogen plus 5-AzaC may be a potential therapeutic strategy for the treatment of androgen-refractory prostate cancer.