5 Alpha-reductase inhibitors: whatʼs new?

Foley, Charlotte; Kirby, Roger

doi:10.1097/00042307-200301000-00006

Cited by 48 publications

(33 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These epithelial cells were cultured in WAJC 404 medium (GIBCO) supplemented with 10% heatinactivated FBS, 25 U/mL of penicillin, 25 g/mL of streptomycin, 28 mM of N-2-hydroxyethyl piperazine-NЈ-2-ethane sulphonate, 14.2 mM of NaHCO 3, 20 ng/mL of cholera toxin, 1 M of dexamethazone, 25 ng/mL of zinc-stabilized insulin, 2.5 M of hydrocortisone, and 250 g/mL of amphotericin B. Fibroblast aggregates, which were removed from the supernatant fluid by an additional centrifugation step at 2000 revolutions per minute for 10 minutes, then were grown in RPMI-1640 medium supplemented with 10% heatinactivated FBS, 50 U/mL of penicillin, 50 g/mL of streptomycin, 10 mM of L-glutamine, and 500 g/mL of amphotericin B. The established primary cell lines were sustained only from 6 to 8 weeks and were passaged either 25-cm 3 or 75-cm…”

Section: Cell Culturementioning

confidence: 99%

Effects of the dual 5 α‐reductase inhibitor dutasteride on apoptosis in primary cultures of prostate cancer epithelial cells and cell lines

McCrohan

Morrissey

O’Keane

et al. 2006

Cancer

View full text Add to dashboard Cite

BACKGROUNDThe profound reduction in serum dihydrotestosterone (DHT) observed with the dual 5 α‐reductase inhibitor (5ARI) dutasteride makes it an attractive agent for prostate cancer therapy. The objective of the current study was to determine whether dutasteride would induce apoptosis in a range of prostate epithelial cell lines and primary cultures.METHODSBoth human prostate androgen‐sensitive cell lines (PwR‐1E, PNT‐2, LNCaP, and PC3[AR2]) and an androgen‐independent cell line (PC‐3) were grown to confluence. Primary epithelial cells extracted from fresh prostate cancer radical prostatectomy specimens also were grown to confluence under optimal conditions. Total cellular protein was extracted to confirm cytokeratin 18 and antihuman α‐methylacyl‐CoA racemase (AMACR) expression of the primary cells. Apoptosis was assessed by propidium iodide DNA staining and flow cytometry after 24 hours of culture in from 0 μM to 10 μM of dutasteride.RESULTSDutasteride induced a dose‐dependent increase in apoptosis in the androgen‐sensitive prostate cell lines PwR‐1E, PNT‐2, and LNCaP and in the androgen receptor‐expressing PC3(AR2) cell line. However, there was no significant apoptosis noted in the parental PC‐3 cells. Of 16 primary epithelial cultures that were treated, 7 cultures were induced to undergo apoptosis, and 9 cultures were unresponsive. All primary cultures were positive for cytokeratin 18 expression, confirming their epithelial phenotype. Responder epithelial cells were positive for AMACR expression.CONCLUSIONSThe results of the current study confirmed that dutasteride differentially induced apoptosis in a subset of prostate cell lines and primary prostate epithelial cells. Understanding the cellular phenotype may indicate susceptible cells. Cancer 2006. © 2006 American Cancer Society.

show abstract

Section: Cell Culturementioning

confidence: 99%

Effects of the dual 5 α‐reductase inhibitor dutasteride on apoptosis in primary cultures of prostate cancer epithelial cells and cell lines

McCrohan

Morrissey

O’Keane

et al. 2006

Cancer

View full text Add to dashboard Cite

show abstract

“…Several types of therapeutic agent, such as 5a-reductase inhibitors, are currently available for treating BPH. 2,3 However, despite significant efficacy in BPH therapy, the adverse effects of these drugs should not be overlooked. For example, finasteride, a synthetic 5a-reductase inhibitor used to treat BPH, 4 triggers adverse effects such as gynaecomastia, the impairment of muscle growth and severe myopathy, owing to structural similarities to steroidal hormones.…”

Section: Introductionmentioning

confidence: 99%

Effects of Melandrium firmum methanolic extract on testosterone-induced benign prostatic hyperplasia in Wistar rats

Lee¹,

Shin²,

Seo³

et al. 2012

Asian J Androl

View full text Add to dashboard Cite

Benign prostatic hyperplasia (BPH) is an age-related disease of unknown aetiology characterized by prostatic enlargement coincident with distinct alterations in tissue histomorphology. Instead of therapeutic agents that can cause severe side effects, plant extracts are frequently used to treat BPH. In this study, we investigated whether the Melandrium firmum methanolic extract (MFME) improves BPH, using the testosterone propionate (TP)-induced BPH rat model. Castration was performed via the scrotal route under sodium pentobarbital anaesthesia. BPH in castrated rats was generated via daily subcutaneous injections of TP (3 mg kg 21 ) dissolved in corn oil, for 4 weeks. MFME was administered daily by oral gavage at a dose of 200 mg kg 21 for 4 weeks, along with the TP injections. The control group received injections of corn oil subcutaneously. At the scheduled termination of the experiment, all rats were killed and their prostates weighed; the relative prostate weight (prostate/body weight ratio) was calculated, and histomorphological changes in the prostate were examined. Additionally, we measured the levels of testosterone and dihydrotestosterone (DHT) in the serum and the prostate. Experimentally induced BPH led to marked decreases in the relative prostate weight and the DHT levels in the serum and the prostate. Histologically, BPH was evident in the ventral lobe of the prostate, and MFME treatment suppressed the severity of the lesions. These results indicate that MFME effectively inhibits the development of BPH induced by testosterone in a rat model. Further studies will be needed to identify the compound(s) responsibility for inducing the protective effect against BPH and determine its mechanism of action.

show abstract

“…[10][11][12] Recently, the results of the landmark Medical Therapy Of Prostatic Symptoms (MTOPS) trial, a placebo-controlled study comparing the a 1 -AR antagonist doxazosin, finasteride and their combination in 3047 LUTS/BPH patients with a mean follow-up of 5 y, became available. 21,22 These results indicate that, in the long term, combination therapy is statistically significantly more effective than both monotherapies, in improving urinary symptoms (total I-PSS) and reducing clinical progression. It seems that, in particular, high-risk patients (those with a large prostate volume/high PSA) may benefit from combination therapy.…”

Section: Discussionmentioning

confidence: 91%

A comparison of the efficacy and tolerability of tamsulosin and finasteride in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia

Rigatti

Brausi

Scarpa

et al. 2003

Prostate Cancer Prostatic Dis

View full text Add to dashboard Cite

In this multicentre, double-blind study, patients with LUTS/BPH were randomised to 26 weeks with finasteride 5 mg once daily (n ¼ 204) or tamsulosin 0.4 mg once daily (n ¼ 199). Double-blind treatment was continued for another 26 weeks (total treatment duration: 1 y). The primary efficacy parameter was the difference in mean change in total Symptom Problem Index (SPI) from baseline to end point at week-26 in the intention-to-treat (ITT) and per protocol (PP) populations. Tamsulosin induced a greater improvement in total SPI (À5.2 points or À37%) compared to finasteride (À4.5 points or À31%) at week-26 (P ¼ 0.055 in ITT and P ¼ 0.032 in PP). Tamsulosin improved urinary symptoms (particularly the more bothersome storage symptoms) and flow more quickly than finasteride. The difference was statistically significant for the SPI from week-1 (reduction, respectively, À2.5 vs À1.8 points, P ¼ 0.043) to week-18 and for Q max from week-1 (increase, respectively, 2.3 vs 0.7 ml/s, P ¼ 0.0007) to week-12. Both treatments were well tolerated with a comparable incidence of adverse events, including urinary retention.

show abstract

5 Alpha-reductase inhibitors: whatʼs new?

Abstract: Recent studies have both clarified and extended the roles of 5 alpha-reductase inhibitors in benign prostatic hyperplasia, and these may expand further if chemopreventive abilities are proved. In addition, dual isoenzyme inhibition will soon be available.

Cited by 48 publications

References 37 publications

Effects of the dual 5 α‐reductase inhibitor dutasteride on apoptosis in primary cultures of prostate cancer epithelial cells and cell lines

Effects of the dual 5 α‐reductase inhibitor dutasteride on apoptosis in primary cultures of prostate cancer epithelial cells and cell lines

Effects of Melandrium firmum methanolic extract on testosterone-induced benign prostatic hyperplasia in Wistar rats

A comparison of the efficacy and tolerability of tamsulosin and finasteride in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia

Contact Info

Product

Resources

About