Co‑treatment with triptolide and RSL3 induces hepatocellular carcinoma cell apoptosis and ferroptosis

Area of Science:

• Biochemistry
• Cell Biology
• Oncology

Background:

• Glutathione peroxidase 4 (GPx4) is crucial in inhibiting cell death pathways like apoptosis and ferroptosis by reducing lipid peroxidation.
• Elevated GPx4 protein levels in hepatocellular carcinoma (HCC) cells after triptolide (TPL) treatment suggest potential resistance to TPL-induced cytotoxicity.
• GPx4 activity inhibition is a potential strategy to enhance anti-cancer therapies.

Purpose of the Study:

• To investigate the combined effect of TPL and RSL3 (a GPx4 inhibitor) on HCC cells.
• To determine if co-treatment can overcome TPL resistance by targeting GPx4.
• To explore the induction of apoptosis and ferroptosis in HCC cells.

Main Methods:

• Cell Counting Kit-8 assay for cell viability.
• Flow cytometry for apoptosis analysis.
• Western blot assays to measure GPx4 protein levels.

Main Results:

• Co-administration of TPL and RSL3 significantly promoted HCC cell apoptosis.
• Intracellular reactive oxygen species (ROS) levels were elevated following combination treatment.
• The combined therapy effectively induced ferroptosis in HCC cells.

Conclusions:

• Co-treatment with TPL and RSL3 enhances anti-proliferative efficacy in HCC cells.
• This combination therapy effectively induces both apoptotic and ferroptotic cell death pathways.
• Targeting GPx4 activity alongside TPL treatment presents a promising strategy for HCC therapy.