Expression of apoptosis-regulating genes in the rat prostate following botulinum toxin type a injection

Abstract

BackgroundOnabotulinumtoxin A (OnabotA) injection has been investigated as a novel treatment for benign prostatic enlargement caused by benign prostatic hyperplasia. An OnabotA - induced volume reduction caused by sympathetic fibers impairment has been proposed as a potential mechanism of action. Our aim was to investigate the expression of apoptosis-regulating proteins in the rat prostate following OnabotA intraprostatic injection.MethodsAdult Wistar rats were injected in the ventral lobes of the prostate with 10 U of OnabotA or saline. A set of OnabotA-injected animals was further treated with 0.5 mg/kg of phenylephrine (PHE) subcutaneously daily. All animals were sacrificed after 1 week and had their prostates harvested. Immunohistochemical staining was performed for Bax, Bcl-xL and caspase-3 proteins and visualized by the avidin-biotin method. The optical density of the glandular cells was also determined, with measurement of differences between average optical densities for each group.ResultsSaline-treated animals showed intense epithelial staining for Bcl-xL and a faint labelling for both Bax and Caspase-3. OnabotA-treated rats showed a reduced epithelial staining of Bcl-xL and a consistently increased Bax and Caspase-3 staining when compared with saline-treated animals. PHE-treated animals showed a stronger Bcl-xL staining and reduced staining of both Bax and Caspase-3 when compared to the OnabotA group. Mean signal intensity measurements for each immunoreaction confirmed a significant decrease of the signal intensity for Bcl-xL and a significant increase of the signal intensity for Bax and Caspase 3 in OnabotA-injected animals when compared with the control group. In OnabotA+PHE treated animals mean signal intensity for Bcl-xL, Bax and Caspase 3 immunoreactions was identical to that of the control animals.ConclusionsThese results support the hypothesis that OnabotA activates apoptotic pathways in the rat prostate through a mechanism that involves sympathetic outflow impairment.

Effect of Botulinum Toxin A on Proliferation and Apoptosis in the T47D Breast Cancer Cell Line

“…The morphological changes (cells with a reduced round-shape cellular) occurred early, after 3 h treatment. These specific shapes are well known as the apoptotic volume decrease (AVD) due to massive efflux of K+ and Cl-through their specific channels, leading to water escape from the cytoplasm, the latter being considered as a major hallmark of apoptotic cells (Gorgal et al, 2012;Hasegawa et al, 2012;Yurinskaya et al, 2012). We found BtxA induced cytotoxicity and apoptosis in T47D cells.…”

“…This interest stems from the fact that BtxA inhibits the growth of LNCaP human prostate cancer cells in vitro and in vivo and induces apoptosis in a dose-dependent manner (Mazo et al, 2008;Karsenty et al, 2009;Proietti et al, 2012). Moreover, BtxA has been shown for up-regulate 167 genes and down-regulate 60 genes relevant to focal adhesion, cell adhesion molecules, adherents and gap junction related pathways in carcinoma cell lines (Thirunavukkarasusx et al, 2011;Gorgal et al, 2012;Nam et al, 2012;Tegenge et al, 2012). The * objective of this study was to test the activity of BtxA against breast cancer cell proliferation underlying this phenomenon as a trial for developing a novel functional anticancer drug.…”

Current and potential urological applications of botulinum toxin A

“…44,45 In humans, increases in apoptotic activity at both the epithelial and stromal components of the prostate were noted after BoNTA injections, thus reducing the bulk or anatomic obstructive component of BPH. 46 Significant reductions in the prostatic urethral pressure response to intravenous noradrenaline and electrostimulation have also been noted after BoNTA injection.…”

The non-neuronal and nonmuscular effects of botulinum toxin: an opportunity for a deadly molecule to treat disease in the skin and beyond

“…In rats, intraprostatic BoNT/A injection altered cellular dynamics by inducing apoptosis, inhibiting proliferation and downregulating α1‐adrenergic receptors, which was associated with prostate apoptosis and atrophic change . The toxin‐treated rats showed reduced epithelial staining of Bcl‐xL and consistently increased Bax and caspase‐3 staining when compared with saline‐treated animals …”