Physical plasma-triggered ROS induces tumor cell death upon cleavage of HSP90 chaperone

Area of Science:

• Oncology
• Biochemistry
• Biophysics

Background:

• Heat Shock Protein 90 (HSP90) is vital for protein folding and cancer progression.
• HSP90's regulatory mechanisms and therapeutic targeting remain areas of active research.
• Cold physical plasma is an emerging, less aggressive tumor therapy with potential anti-cancer effects.

Purpose of the Study:

• To investigate the effect of cold physical plasma on HSP90 expression and activity in cancer cells.
• To elucidate the downstream effects of HSP90 modulation by cold plasma.
• To evaluate the synergistic effects of combining cold plasma with HSP90 inhibitors.

Main Methods:

• Cancer cells were treated with cold physical plasma.
• Reactive oxygen species (ROS) generation was measured.
• HSP90 cleavage and client protein degradation (PKD2) were assessed.
• Cell viability was evaluated after combined treatment with cold plasma and PU-H71.

Main Results:

• Cold plasma treatment induced ROS generation, leading to HSP90 cleavage.
• HSP90 cleavage resulted in the degradation of PKD2, a key regulator of tumor growth.
• Pre-sensitization with PU-H71 followed by cold plasma treatment synergistically reduced cancer cell viability.

Conclusions:

• Cold physical plasma effectively targets HSP90 through ROS-mediated cleavage.
• This mechanism impacts downstream effectors like PKD2, crucial for tumor progression.
• Combination therapy with cold plasma and HSP90 inhibitors shows promise for enhanced cancer treatment.