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

Area of Science:

• Molecular Biology
• Cancer Biology
• Mitochondrial Biology

Background:

• Prostate cancer frequently harbors p53 mutations, primarily in the DNA binding domain, correlating with reduced disease-free survival.
• Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a regulator of mitochondrial function, is highly expressed in p53-mutated prostate cancer cells.

Purpose of the Study:

• To investigate the regulatory role of p53 on PGC-1α expression and mitochondrial function in prostate cancer cells.
• To explore the therapeutic potential of targeting the p53/PGC-1α pathway in prostate cancer.

Main Methods:

• p53 overexpression was induced in PC3 prostate cancer cells.
• PGC-1α expression, nuclear localization, and mitochondrial function were assessed.
• PGC-1α activation using ZLN005 was employed to study effects on mitochondrial function and apoptosis.

Main Results:

• p53 overexpression decreased PGC-1α expression and nuclear localization, leading to mitochondrial dysfunction.
• Activation of PGC-1α partially ameliorated p53-induced mitochondrial dysfunction.
• The p53/PGC-1α pathway inhibition affected mitochondrial biogenesis and dynamics, contributing to mitochondrial dysfunction and apoptosis in PC3 cells.

Conclusions:

• p53 negatively regulates PGC-1α, inducing mitochondrial dysfunction and promoting apoptosis in prostate cancer cells.
• PGC-1α is a critical mediator of p53-induced apoptosis in prostate cancer.
• Targeting the p53/PGC-1α pathway presents a promising therapeutic strategy for prostate cancer treatment.