Caffeic acid phenethyl ester guards against benign prostate hypertrophy in rats: Role of IGF‐1R/protein kinase‐B (Akt)/β‐catenin signaling

Abstract

Benign prostate hypertrophy (BPH) is among the most common diseases with a huge impact on the quality of life of elderly men. There is a current need for the development of well-tolerated and effective preventive strategies to improve the clinical outcome. Caffeic acid phenethyl ester (CAPE) is an important active ingredient isolated from honey-bee propolis with potent anti-proliferative, anti-inflammatory and antioxidant effects. These properties promote CAPE as a promising candidate to be tested as an alternative therapy for BPH, which is still uninvestigated. Herein, we tested the ability of CAPE to guard against testosterone-induced BPH and investigated the involvement of IGF1-R/Akt/β-catenin signaling as a protective mechanism in testosterone-induced BPH rat model. Treatment with CAPE reduced testosterone-induced increase in the prostate index and histopathological alterations. In addition, co-treatment with CAPE significantly suppressed insulin-like growth factor-1 receptor (IGF-1R)/Akt/β-catenin/cyclinD1 axis as well as tumor necrosis factor-α level and nuclear factor (NF)-kB activity. Furthermore, the treatment with CAPE replenished the antioxidant defense systems, superoxide dismutase (SOD) and reduced glutathione (GSH) with subsequent reduction in prostate tissue lipid peroxides. This study highlights the potential merit of CAPE-enriched propolis formulations to protect elderly men against the development of BPH. © 2018 IUBMB Life, 70(6):519-528, 2018.

Comparative RNA-sequencing analysis of the prostate in a mouse model of benign prostatic hyperplasia with bladder outlet obstruction

“…Oxidative stress is also considered to be one of the mechanisms that cause early pathological changes during prostate hyperplasia [ 60 ]. Oxidative stress can promote prostate hyperplasia by affecting the apoptosis pathway of prostate cells [ 61 ], inducing prostatitis [ 62 , 63 ], and accelerating prostate proliferation [ 64 ] by activating the PI3K/Akt signalling pathway. Androgen can induce oxidative stress by increasing free radicals [ 65 ] and physiological amount of estrogen has antioxidant effect, but over-physiological amount of estrogen may induce oxidative stress by causing mitochondrial dysfunction [ 66 ].…”

“…It is known that the development of BPH is dependent on steroid hormones [ 79 ]. The key genes IGF1 and EPHA7, important seed genes in the modules and hub genes in several algorithms, were also identified, and previous studies have shown that IGF1 is associated with the development of BPH [ 64 , 80 , 81 ]. Findings involving EPHA7 have not been reported in most studies of BPH, although one study found that EPHA7 expression was upregulated in BPH tissue or normal tissue compared to most PCa samples [ 82 ].…”

Comparative RNA-sequencing analysis of the prostate in a mouse model of benign prostatic hyperplasia with bladder outlet obstruction

“…It was known that the development of BPH was dependent on steroid hormones 55 . The key genes IGF1 and EPHA7, important seed genes in the modules and hub genes in several algorithms, were also obtained, and previous studies have shown that IGF1 is associated with the development of BPH [56][57][58] . While EPHA7 had not been reported in studies of BPH, and one study found EPHA7 expression was upregulated in BPH tissue or normal tissue compared to most PCa samples 59 .…”

Qianliexin capsule exerts anti‐inflammatory activity in chronic non‐bacterial prostatitis and benign prostatic hyperplasia via NF‐κB and inflammasome

“…The constituents of QLX include numerous polyphenols and polyphenolic metabolites such as caffeic acid, gallic acid, p ‐coumaric acid, protocatechuic acid, neochlorogenic acid and chlorogenic acid. Dietary polyphenols are known to benefit management of BPH and CNP 35‐37 . The evidence suggested that QLX exerts a prostatic protective function and might be used to relieve LUTS associated with CNP and BPH.…”