Finasteride Increases the Expression of Hemoxygenase-1 (HO-1) and NF-E2-Related Factor-2 (Nrf2) Proteins in PC-3 Cells: Implication of Finasteride-Mediated High-Grade Prostate Tumor Occurrence.
- Author:
Do Kyung YUN
1
;
June LEE
;
Young Sam KEUM
Author Information
1. Department of Biochemistry, College of Pharmacy, Dongguk University, Goyang 410-820, Republic of Korea. keum03@dongguk.edu
- Publication Type:Original Article
- Keywords:
Chemoprevention;
Finasteride;
5alpha-reductase (5-AR);
NF-E2-related factor-2 (Nrf2)
- MeSH:
Apoptosis;
Carcinogenesis;
Chemoprevention;
Finasteride*;
Hand;
Humans;
Incidence;
Male;
Prostate*;
Prostatic Neoplasms;
Proto-Oncogenes;
Up-Regulation
- From:Biomolecules & Therapeutics
2013;21(1):49-53
- CountryRepublic of Korea
- Language:English
-
Abstract:
A number of naturally-occurring or synthetic chemicals have been reported to exhibit prostate chemopreventive effects. Synthetic 5alpha-reductase (5-AR) inhibitors, e.g. finasteride and durasteride, gained special interests as possible prostate chemopreventive agents. Indeed, two large-scale epidemiological studies have demonstrated that finasteride or durasteride significantly reduced the incidence of prostate cancer formation in men. However, these studies have raised an unexpected concern; finasteride and durasteride increased the occurrence of aggressive prostate tumor formation. In the present study, we have observed that treatment of finasteride did not affect the growth of androgen-refractory PC-3 prostate cancer cells. Finasteride also failed to induce apoptosis or affect the expression of proto-oncogenes in PC-3 cells. Interestingly, we found that treatment of finasteride induced the expression of Nrf2 and HO-1 proteins in PC-3 cells. In particular, basal level of Nrf2 protein was higher in androgen-refractory prostate cancer cells, e.g. DU-145 and PC-3 cells, compared with androgen-responsive prostate cancer cells, e.g. LNCaP cells. Also, treatment of finasteride resulted in a selective induction of Nrf2 protein in DU-145 and PC-3 cells, but not in LNCaP cells. In view of the fact that upregulation of Nrf2-mediated phase II cytoprotective enzymes contribute to attenuating tumor promotion in normal cells, but, on the other hand, confers a selective advantage for cancer cells to proliferate and survive against chemical carcinogenesis and other forms of toxicity, we propose that finasteride-mediated induction of Nrf2 protein might be responsible, at least in part, for an increased risk of high-grade prostate tumor formation in men.
