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

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.

Oncotarget. 2017 Aug 03*** epublish ***

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

Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Dongdaemun-Gu, Seoul 02447, Republic of Korea., Basic Research Laboratory for Comorbidity Regulation, College of Korean Medicine, Kyung Hee University, Dongdaemun-Gu, Seoul 02447, Republic of Korea., Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore., Department of Herbology, College of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 54538, Republic of Korea.