Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Finasteride is widely used in treatment of symptomatic benign prostatic hyperplasia. Treatment of rats with finasteride caused a significant decrease in ventral prostate weight and intraprostatic dihydrotestosterone levels while intraprostatic testosterone levels were increased. Finasteride inhibited Akt-1 and MAPK expression while expression of PTEN was significantly increased only at 100 mg dose. Basal phosphorylation of c-Raf, MEK1/2, MAPK and the transcription factor Elk-1 was significantly reduced by finasteride. The rate of prostate epithelial apoptosis is equivalent to 0.1+/-0.03, 0.6+/-0.18%, 0.92+/-0.24% and 1.42+/-0.3% on treatments with 0, 1, 10 and 100 mg finasteride per kg body weight, respectively. Concomitantly, these treatments led to a 2.5-, 4.0- and 4.0-fold increase in Bad while a slight decrease in Bax was observed. Similar elevations were also observed in Bcl-xs levels which increased by 9.8-, 10- and 12-fold respectively in the finasteride treatments as compared to controls. Bcl-xL levels in ventral prostates treated with 1, 10 and 100 mg finasteride were approximately 30, 30 and 26% of control, respectively. Significant reduction in Bcl-2 expression was observed only at the dose of 100 mg/kg body weight. These findings suggest that modulation of MAP kinase and Akt expression, Bcl-xL, Bcl-xs, Bcl-2 and Bad proteins by finasteride may be, in part, responsible for the anti-proliferative and apoptotic effect of this drug seen clinically and in animal models.
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PMID:Induction of apoptosis in rat ventral prostate by finasteride is associated with alteration in MAP kinase pathways and Bcl-2 related family of proteins. 1201 13

Previous studies by our group showed that Qianliening capsules (QC), a clinically proven effective traditional Chinese formulation that has long been used in the treatment of benign prostatic hyperplasia (BPH), is capable of inhibiting BPH in vivo and in vitro via the promotion of apoptosis, suppression of the EGFR/STAT3 signaling pathway and regulating the expression of sex hormones as well as their receptors. However, the mechanism of its anti-BPH activity has remained to be fully elucidated. The present study aimed to investigate the mechanism underlying the anti-proliferative effect of QC in vivo and in vitro. Castrated male Sprage-Dawley (SD) rats where subcutaneously injected with testosterone propionate and the WPMY-1 cell line was stimulated with basic fibroblast growth factor in order to generate BPH in vivo and in vitro separately, both of which were then subjected to QC treatment. Finasteride was used as a positive control drug for the in vivo study. In the present study, it was found that treatment with QC or finasteride significantly reduced the prostatic index (PI=prostate wet weight/body weight x 100) in a rat model of BPH (P<0.05). In addition, reverse transcription quantitative polymerase chain reaction (RT-PCR) and western blot analyses showed that QC or finasteride treatment significantly inhibited model construction-induced upregulation of expression of proliferating cell nuclear antigen, cyclin D1 and cyclin-dependent kinase 4 in prostatic tissues of rats with BPH (P<0.05). The in vitro study further proved that QC exhibited anti-proliferative properties via G1/S cell cycle arrest in the WPMY-1 cell line, as evidenced by colony formation, flow cytometric cell cycle, immunoblot and RT-PCR analyses. In conclusion, the present study demonstrated that inhibition of cell proliferation via G1/S cell cycle arrest may be one of the underlying mechanisms of the effect of QC on BPH.
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PMID:Anti-proliferative effects of qianliening capsules on prostatic hyperplasia in vitro and in vivo. 2582 41