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

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.

The relationship between headache, depressive tendency and family function-in high school girls in Seoul-

BACKGROUND: Headache is one of the most common symptoms having experienced by many people. High school girls are expected to experience headache very often. Their proper treatment and adequate medical service is doubtful, and stressful environment of the Korean high school will augment the chronicity of headache. Knowing the forms of headache and categorizing the headache according to headache classification system is important for proper treatment of headache. Types of headache in high school girls have been categorized using International Headache Society (IHS) system. The relationships of headache with Beck Depression Inventory (BDI) and Family APGAR score of the headache groups and control group are investigated. Thus, the purpose of this study was to attribute to the treatment of the headache in female youths. METHODS: The questionnaires .on headache, under direct interviews, was given to each high school girls in Seoul, from March 1 to 31, 1999. The headache group was subclassified into migraine group, tension headache group and other headache group, using IHS system. Furthermore, the migraine group was subclassified into migraine with aura (classic migraine), migraine without aura (common migraine) and other migronous disorder. The students who had not experienced any headaches during the recent one year have been selected as the normal group. The normal group was compared with the headache group, i.e., tension headache and migraine. Depressed tendency was assessed using the BDI; and family function was evaluated by Family APGAR. The data are analyzed using SPSS 8.0. RESULTS: Among the subjects, 304 (60.4%) high school girls had experienced a headache during the previous one year. The girls with migraine, tension headache, and other types of headache were 110 (38%), 81 (27%) and 113 (35%), respectively. The migraine group showed higher BDI scores (p0.05) CONCLUSIONS: When the headache in high school girls was classified by using IHS system, headache in the migraine group was more prevalent than in the tension headache group and normal group. And the migraine group had more depressive tendency. When physicians deal with the headache in high school girls, they need to be aware of migraine headache and associated depressive tendency.