Vanillic acid attenuates testosterone-induced benign prostatic hyperplasia in rats and inhibits proliferation of prostatic epithelial cells.

Yunu Jung,Kwang Seok Ahn,Hye-Lin Kim,Jinbong Park,Mi-Young Jeong,Sung-Joo Park,Seona Lim,Jae-Young Um,Jongwook Kang,Dong-Hyun Youn,Gautam Sethi

doi:10.18632/oncotarget.19909

Yunu Jung, Kwang Seok Ahn + Show 9 more

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https://doi.org/10.18632/oncotarget.19909

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Abstract

Benign prostatic hyperplasia (BPH) is a common disease in the male population, especially in elderly men. Vanillic acid (VA), a dihydroxybenzoic derivative used as a flavoring agent, is reported to have an anti-inflammatory effect. However, there are no reports of its effects on BPH to date. BPH was induced with a pre-4-week treatment of daily subcutaneous injections of testosterone propionate (TP), and the normal control group received injections of ethanol with corn oil instead. Six weeks of further injections were done with (a) ethanol with corn oil, (b) TP only, (c) TP + finasteride, and (d) TP + VA. Finasteride was used as a positive control group. VA had protective effects on the TP-induced BPH. In the VA treatment group, the prostate weight was reduced, and the histological changes including the epithelial thickness and lumen area were restored like in the normal control group. Furthermore, in the VA treatment group, two proliferation related factors, high molecular weight cytokeratin 34βE12 and α smooth muscle actin, were significantly down-regulated compared to the TP-induced BPH group. The expressions of dihydrotestosterone and 5α-reductase, the most crucial factors in BPH development, were suppressed by VA treatment. Expressions of the androgen receptor, estrogen receptor α and steroid receptor coactivator 1 were also significantly inhibited by VA compared to the TP-induced BPH group. In addition, we established an in vitro model for BPH by treating a normal human prostatic epithelial cell line RWPE-1 with TP. VA successfully inhibited proliferation and BPH-related factors in a concentration-dependent manner in this newly established model. These results suggest a new and potential pharmaceutical therapy of VA in the treatment of BPH.

Highlights

Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases in the male population, in which the incidence increases gradually with age, and almost 50% of men over 50 suffer from BPH symptoms [1]
There was no significant difference in the body weights of the rats regardless of the testosterone propionate (TP) treatment
While Vanillic acid (VA) is a compound derived from Angelica sinensis, olives [51], rice [52], ginsengs [53], acai fruits [54], and various kinds of berries are rich in VA [55]

Summary

Introduction

Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases in the male population, in which the incidence increases gradually with age, and almost 50% of men over 50 suffer from BPH symptoms [1]. Testosterone and DHT both bind to the same receptor, AR, which results in increased transcription of androgendependent genes and stimulate protein synthesis [9]. This specific receptor, AR, is a type of nuclear receptor that is activated by the binding of androgens in the cytoplasm which are translocated into the nucleus [10]. Expressions of androgen-regulated genes are affected by co-regulators including steroid receptor coactivator 1 (SRC-1), which modify the transcriptional activity of AR which could be related to BPH [11]. In addition to the 5AR-AR pathway, estrogen receptors (ERs) α and β are known to regulate prostatic proliferation [12]

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