NEK6 Regulates Redox Balance and DNA Damage Response in DU-145 Prostate Cancer Cells

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• Castration-resistant prostate cancer (CRPC) cells exhibit high reactive oxygen species (ROS) levels and enhanced antioxidant defenses to survive.
• The precise pathways regulated by NEK6 kinase in CRPC progression remain largely unknown.

Purpose of the Study:

• To investigate the role of NEK6 in regulating redox state, DNA damage response, and cell viability in CRPC DU-145 cells.
• To explore the potential of NEK6 as a therapeutic target in CRPC.

Main Methods:

• NEK6 gene knockout in DU-145 cells.
• Evaluation of intracellular ROS levels, antioxidant enzyme expression (SOD1, SOD2, PRDX3), DNA damage markers (p-ATM, γH2AX), JNK phosphorylation, and apoptosis.
• Assessment of cell viability, clonogenic capacity, mitochondrial activity, and sensitivity to cisplatin.

Main Results:

• NEK6 knockout decreased clonogenic capacity, proliferation, cell viability, and mitochondrial activity.
• NEK6 depletion increased intracellular ROS, decreased antioxidant defenses, elevated JNK phosphorylation, and augmented DNA damage markers.
• NEK6 absence induced apoptosis, reduced Bcl-2 expression, and sensitized cells to cisplatin, also affecting NF-κB2 nuclear localization.

Conclusions:

• NEK6 plays a critical role in maintaining redox balance and suppressing DNA damage in CRPC cells.
• NEK6 inhibition disrupts these protective mechanisms, leading to increased ROS, DNA damage, and apoptosis.
• Targeting NEK6 represents a promising therapeutic strategy for castration-resistant prostate cancer.