Crosstalk between apoptosis and autophagy in prostate epithelial cells under androgen deprivation

Abstract

The present study investigated the molecular mechanism of apoptosis and autophagy in prostate epithelial cells under androgen deprivation (AD). BPH-1 cells were divided into four groups as follows: Control (Cont), AD, autophagy inhibition (AI) and AD + AI groups. Cells in the four groups were treated accordingly, and the level of apoptosis was subsequently measured via flow cytometry. The expression of the microtubule-associated proteins 1A/1B light chain 3 (LC3), caspase-3, poly (ADP-ribose) polymerase 1 (PARP-1) and Beclin-1 proteins of BPH-1 cells was detected at different time points following culture in androgen-deprived medium. Western blotting revealed that the basal levels of the LC3-II protein were detected at 0 h. At 4 h, LC3-II was significantly increased compared with 0 h (P<0.05). Beginning at 20 h, the expression level of the LC3-II protein decreased significantly (P<0.05). Western blotting revealed that beginning at 24 h, the expression level of the PARP-1 protein decreased significantly (P<0.001) and the cleavage fragments of the PARP-1 protein appeared. These results further imply that autophagy serves a cell protective function by mutual inhibition with apoptosis in BPH-1 cells in the removal of androgen conditions. Furthermore, the fragments of the cleaved Beclin-1 protein appeared as 35 and 37 kDa bands. Flow cytometry analysis demonstrated that the rate of cell apoptosis in the AD, AI and AD + AI groups was significantly increased compared with the Cont group (P<0.01). Compared with the AD or the AI groups individually, the rate of cell apoptosis in the AD + AI group was significantly increased (P<0.001). These findings suggest that in the early stage of AD, autophagy has a compensatory function in the cell, whereas in the whole process, autophagy and apoptosis share a mutual antagonism. The Beclin-1-C protein fragment contributed positive feedback to the process of apoptosis, which may be a potential mechanism of AD therapy. Therefore, AD and AI exhibit a synergistic effect to further improve the level of apoptosis.

Glutathione Peroxidase 3 induced mitochondria-mediated apoptosis via AMPK /ERK1/2 pathway and resisted autophagy-related ferroptosis via AMPK/mTOR pathway in hyperplastic prostate

“…Interestingly, our data observed that GPX3 had the pro-apoptosis but anti-autophagy-related ferroptosis effect in prostate cells. Study had shown that autophagy inhibition could enhance the apoptosis induced by androgen deprivation in human BPH-1 cells [ 68 ]. In this study, both in human prostate tissues and in the prostate of T-BPH rats, there were inhibition of apoptosis and abnormal activation of autophagy, as well as increased ferroptosis levels (in an autophagy-related manner).…”

Uncovering the Secrets of Prostate Cancer’s Radiotherapy Resistance: Advances in Mechanism Research

“…Furthermore, recent clinical research has also demonstrated that the local failure rate of CRPC after local treatment is significantly higher than that of hormone-sensitive PCa [ 6 ], indicating that the radiosensitivity of PCa is reduced when the PCa is transformed from an androgen-dependent state to an androgen-independent state. In terms of drug mechanism, theoretically, ADT could have a synergistic effect with radiotherapy for PCa because it can induce the apoptosis and autophagy of PCa cells [ 17 ]. In addition, androgen-sensitive PCa LNCaP cells expressing AR undergo a higher rate of radiation-induced apoptosis in the absence of androgens [ 18 ], which is consistent with findings from other studies.…”

Inhibiting CBP Decreases AR Expression and Inhibits Proliferation in Benign Prostate Epithelial Cells

“…Benign prostatic hyperplasia (BPH) is a common disease in elderly men [1]. Since pathogenic factors induce BPH by disrupting the meticulous balance between the proliferation and apoptosis of prostate epithelial cells [2], studying the regulation of proliferation and apoptosis in prostate epithelial cells is of great significance for BPH. Thus far, although various studies have reported that the GRP78, NELL2, METTL3/YTHDF2/PTEN signaling pathways, DNA methylation, and others may play roles in regulating the proliferation and apoptosis of prostate epithelial cells [3][4][5], androgens and androgen receptors (AR) remain the key in the proliferation and apoptosis of prostate epithelial cells in BPH [6].…”