Inhibition of androgen induces autophagy in benign prostate epithelial cells

Abstract

Abbreviations & Acronyms 3-MA = 3-methyladenine 5-ARI = 5-α reductase inhibitor AD = androgen deprivation medium BPH = benign prostatic hyperplasia CM = complete medium DAPI = 4, 6-diamidino-2-phenylindole Objective: 5-α Reductase inhibitor can reduce the volume of benign prostatic hyperplasia by lowering benign prostatic hyperplasia level and consequently inducing epithelial cells apoptosis. The present study investigated whether autophagy and apoptosis of benign prostatic hyperplasia epithelial cells are influenced by low benign prostatic hyperplasia levels. Methods: PWR-1E prostate epithelial cells transfected with GFP-LC3 plasmid were subjected to androgen deprivation conditions. Then the autophagic puncta were evaluated by fluorescence microscopy, and the cellular apoptosis rate was detected by 4, 6-diamidino-2-phenylindole staining after blocking of autophagic process by 3-methyladenine. Furthermore, autophagy status was also determined in hyperplasia prostate tissues from 5-α reductase inhibitor-treated patients by immunohistochemistry. Results: In the androgen deprivation medium, autophagic punta increased markedly in PWR-1E cells, and blockage of autophagy by 3-methyladenine significantly promoted PWR-1E cells' apoptosis rate. In vivo, the expression of LC3 protein (an important autophagic marker) in hyperplasia prostate tissue significantly increased after 5-α reductase inhibitor treatment. Meanwhile, the prostate-specific antigen, as an inner control, decreased. Conclusion: 5-α Reductase inhibitor treatment increases autophagy and possibly decreases the apoptosis of prostate epithelial cells.

Di-n-butyl phthalate induced hypospadias relates to autophagy in genital tubercle via the PI3K/Akt/mTOR pathway

“…In androgen-sensitive cells, such as prostate epithelial cells, the androgen signaling pathway is closely associated with autophagy, which affects cell survival (Boutin et al 2013;Li et al 2014). Autophagy is the major intracellular degradation and recycling system, which plays an important role in the turnover of unnecessary or dysfunctional proteins and organelles.…”

“…These cellular constituents are sequestered in double-or multiple-membranes vacuoles called autophagosomes, which subsequently fuse with lysosomes and are degraded by hydrolases (Cuervo 2004;Galluzzi et al 2008). Prostate cancer cells (HRPCa cells) (Boutin et al 2013) and benign prostate epithelial cells (Li et al 2014) show significantly elevated autophagy after androgen deprivation. The present study found significantly decreased levels of testosterone in male rats after DBP treatment.…”

“…Autophagy serves an important cross talking point between type 1 and type 2 cell death pathways, and inhibition of autophagy can trigger apoptosis ( Boya et al 2005 ) . Androgen deprivation can increase autophagy, while inhibition of autophagy by 3-methyladenine can promote apoptosis in androgen sensitive benign prostate epithelial cells (Li et al 2014 ) . However, the roles of autophagy and apoptosis in the pathogenesis of hypospadias induced by DBP are not clear.…”

5‐ARI induces autophagy of prostate epithelial cells through suppressing IGF‐1 expression in prostate fibroblasts

“…13 To do this, we first evaluate autophagy levels in prostate specimens from patients who received 5-ARI. 13 To do this, we first evaluate autophagy levels in prostate specimens from patients who received 5-ARI.…”

“…9 Autophagy often exerts cytoprotective functions to sustain the reestablishment of the cell status. 13 Thus, we hypothesized that autophagy might lead to prostate epithelial cell proliferation and BPH progression after long-term 5-ARI treatment. 10 Another study has also shown that hypoxia-induced autophagy promotes the survival of human prostatic cells.…”