p53/PGC‑1α‑mediated mitochondrial dysfunction promotes PC3 prostate cancer cell apoptosis

Li,Jiuling; Li,Yany; Chen,Lanlan; Yu,Bingbing; Xue,Yanan; Guo,Rui; Su,Jing; Liu,Yanan; Sun,Liankun

doi:10.3892/mmr.2020.11121

p53/PGC‑1α‑mediated mitochondrial dysfunction promotes PC3 prostate cancer cell apoptosis

Authors:
- Jiuling Li
- Yany Li
- Lanlan Chen
- Bingbing Yu
- Yanan Xue
- Rui Guo
- Jing Su
- Yanan Liu
- Liankun Sun
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Affiliations: Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Center, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China, School of Clinical Medicine, Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: May 5, 2020 https://doi.org/10.3892/mmr.2020.11121
Pages: 155-164
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Data for p53 mutation in prostate cancer in The Cancer Genome Atlas database revealed that >85% of p53 mutations occurred in the p53 DNA binding domain. These mutations not only severely damage the function of the p53 protein, but also reduce the disease‑free survival of patients. Peroxisome proliferator‑activated receptor γ coactivator‑1α (PGC‑1α) is involved in the regulation of mitochondrial function and is highly expressed in prostate cancer PC3 and DU145 cells with p53 deletion or mutation. However, whether p53 negatively regulates PGC‑1α in prostate cancer cells remains to be elucidated. In the present study, p53 overexpression was induced in prostate cancer PC3 cells. Subsequently, the expression levels of PGC‑1α and alterations to mitochondrial function were assessed. Moreover, PGC‑1α was activated in prostate cancer PC3 cells using ZLN005 to investigate alterations to mitochondrial function and cell apoptosis. The present study revealed that p53 decreased the expression and nuclear localization of the PGC‑1α protein and induced mitochondrial dysfunction. Activation of PGC‑1α partially reversed p53‑mediated mitochondrial dysfunction. Inhibition of the p53/PGC‑1α pathway on mitochondrial biogenesis and fission‑/fusion‑associated gene and protein expression were associated with mitochondrial dysfunction. p53/PGC‑1α‑mediated mitochondrial dysfunction promoted apoptosis of PC3 prostate cancer cells. The results indicated that PGC‑1α is an essential target of p53‑induced apoptosis in prostate cancer cells and indicated that targeting PGC‑1α may provide a new therapeutic strategy for prostate cancer.

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