Human Castration Resistant Prostate Cancer Rather Prefer to Decreased 5α-reductase Activity

Overview

Journal Sci Rep

Specialty Science

Date 2013 Feb 23

PMID 23429215

Citations 10

Authors

Takeo Kosaka

Akira Miyajima

Hirohiko Nagata

Takahiro Maeda

Eiji Kikuchi

Mototsugu Oya

Affiliations

Soon will be listed here.

Abstract

Physiologically relevant steroid 5α-reductase (SRD5A) activity that is essential for dihydrotestosterone (DHT) biosynthesis in human castration-resistant prostate cancer (CRPC) has not been fully characterized yet. In this study to ascertain the potential SRD5A activity, we cultured two human CRPC cell lines, C4-2 and C4-2AT6, with the steroid precursor: ¹³C-[2,3,4]-androstenedione (13C-Adione), and analyzed the sequential biosynthesis of ¹³C-[2,3,4]-testosterone (13C-T) and ¹³C-[2,3,4]-DHT (13C-DHT) by liquid chromatography/mass spectrometry (LC/MS/MS). The 13C-DHT/13C-T concentration ratio detected by LC/MS/MS in C4-2AT6 cells appeared to reflect the SRD5A activity. The ratio in C4-2AT6 was significantly lower than that in C4-2. An increased concentration of DHT did not have a positive effect on cell proliferation, rather it exhibited inhibitory effects. 5α-reductase inhibitors did not have any inhibitory effect at clinically achievable concentrations. These results indicate that CRPC cells may have an unknown regulation system to protect themselves from an androgenic suppressive effect mediated by SRD5A activity.

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