Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia

Abstract

Benign prostatic hyperplasia (BPH) is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and networks underlying the development and the progression of the disease are still far from being fully understood. BPH results from smooth muscle cell and epithelial cell proliferation, primarily within the transition zone of the prostate. Apoptosis and inflammation play important roles in the control of cell growth and in the maintenance of tissue homeostasis. Disturbances in molecular mechanisms of apoptosis machinery have been linked to BPH. Increased levels of the glycoprotein Dickkopf-related protein 3 in BPH cause an inhibition of the apoptosis machinery through a reduction in B cell lymphoma (Bcl)-2 associated X protein (Bax) expression. Inhibitors of apoptosis proteins influence cell death by direct inhibition of caspases and modulation of the transcription factor nuclear factor-κB. Current pharmacotherapy targets either the static component of BPH, including finasteride and dutasteride, or the dynamic component of BPH, including α-adrenoceptor antagonists such as tamsulosin and alfuzosin. Both these classes of drugs significantly interfere with the apoptosis machinery. Furthermore, phytotherapic supplements and new drugs may also modulate several molecular steps of apoptosis.

<i>Quisqualis indica</i> Improves Benign Prostatic Hyperplasia by Regulating Prostate Cell Proliferation and Apoptosis

“…Various diseases, including BPH, are characterized by disruption of processes that regulate cell proliferation and cell death. 40,41) Epithelial cells in normal prostate tissue express little or no Bcl-2 or caspase-3, but hyperplastic changes are associated with increased levels of Bcl-2 and a decreased levels of Bax in the prostate. 42,43) The Bcl-2/Bax ratio is an important measure of cell fate, and an increased ratio (resulting from aberrant expression of these proteins) is common in BPH.…”

Anti-Proliferative Effects of HBX-5 on Progression of Benign Prostatic Hyperplasia

“…As part of the efforts to substitute synthetic medications and minimize the side effects, phytotherapy has been gaining attention. Recently, phytotherapy represented more than 90% of all the treatments prescribed for BPH in Germany and Austria, and its use has increased considerably in the USA [ 32 ]. Accordingly, many studies have been conducted to assess the clinical evidence on the alternative treatment for BPH [ 33 ].…”

Qianlongtong Inhibits Proliferation and Induces Apoptosis of Hyperplastic Prostate Cells

“…Among them, Bcl-2 and Bax are considered to be the most important regulatory genes involved in the apoptosis of prostate tissues. It is believed that many biological molecules are involved in the process of apoptosis, in which caspases are the key executors of apoptosis ( Minutoli et al, 2016 ).…”

“…Many molecules might be involved in this process. Traditionally, p15, p18, p21, and p27 are regarded as antiproliferative molecules, and cyclin B, cyclin D, cyclin E, as well as cdk2 and cdk4 are regarded as pro-proliferative molecules ( Fang, DeMarco, & Nicholl, 2012 ; Fang et al, 2007 ; Griffith, Brunner, Fletcher, Green, & Ferguson, 1995 ; Karimian, Ahmadi, & Yousefi, 2016 ; Minutoli et al, 2016 ; Ohkoshi, Yano, & Matsuda, 2015 ; Ohtsubo, Theodoras, Schumacher, Roberts, & Pagano, 1995 ; Sharma & Pledger, 2016 ; Sherr, 1994 ; Zhu et al, 2017 ). It will be necessary to investigate the change in these molecules caused by Qianlongtong; such a project is underway with plans to summarize the findings in a separate article.…”