Monitoring of Propiolamide-Mediated Molecular Crosstalk between Ferroptosis and Apoptosis by Raman Spectroscopy

Area of Science:

• Biochemistry
• Molecular Biology
• Chemical Biology

Background:

• Programmed cell death is crucial for cancer treatment.
• Understanding cell death pathways aids anticancer drug design.
• Ferroptosis and apoptosis are key cell death mechanisms.

Purpose of the Study:

• Investigate the crosstalk between ferroptosis and apoptosis mediated by propiolamides.
• Reveal the molecular mechanisms of propiolamides in inducing cell death.
• Develop an in situ monitoring strategy for enzyme-drug interactions.

Main Methods:

• Utilized Raman spectroscopy for in situ monitoring of reactive oxygen species (ROS) and propiolamide structural changes.
• Investigated the inhibition of GPX4 activity by propiolamides.
• Analyzed the pro-ferroptotic and pro-apoptotic roles of terminal alkyne-containing propiolamides.

Main Results:

• Propiolamides induce monooxygenase-mediated ROS generation.
• Propiolamides inhibit GPX4 activity, promoting ferroptosis.
• Terminal alkyne-containing propiolamides exhibit both pro-ferroptotic and pro-apoptotic effects.
• Developed a label-free method for monitoring enzyme-drug dynamics.

Conclusions:

• Propiolamides effectively trigger a crosstalk between ferroptosis and apoptosis.
• This study provides insights into the structural basis of enzyme-drug interactions in cell death.
• Paves the way for designing novel anticancer drugs with synergistic cell death induction.