Bavachin Induces Ferroptosis through the STAT3/P53/SLC7A11 Axis in Osteosarcoma Cells

Area of Science:

• Biochemistry
• Cell Biology
• Oncology

Background:

• Ferroptosis is an iron-dependent form of regulated cell death.
• Bavachin exhibits anti-tumor effects and increases reactive oxygen species (ROS).
• The role of bavachin in inducing ferroptosis in osteosarcoma (OS) cells is not well understood.

Purpose of the Study:

• To investigate whether bavachin can induce ferroptosis in osteosarcoma cells.
• To elucidate the underlying molecular mechanisms of bavachin-induced ferroptosis in OS.

Main Methods:

• Assessing cell viability, iron levels, ROS, malondialdehyde, and glutathione in OS cell lines (MG63 and HOS) treated with bavachin.
• Utilizing iron chelators, antioxidants, and ferroptosis inhibitors to validate the mechanism.
• Analyzing mitochondrial morphology via electron microscopy.
• Quantifying the expression of key proteins and genes involved in iron metabolism, oxidative stress, and cell death pathways (e.g., transferrin receptor, DMT-1, P53, ferritin, STAT3, SLC7A11, GPX4).

Main Results:

• Bavachin inhibited OS cell viability, increased intracellular iron, ROS, and malondialdehyde, while depleting glutathione.
• Iron chelators, antioxidants, and ferroptosis inhibitors reversed bavachin-induced cell death.
• Bavachin treatment altered mitochondrial morphology and modulated the expression of proteins involved in iron transport, P53 signaling, and ferroptosis, including upregulation of transferrin receptor, DMT-1, and P53, and downregulation of ferritin, p-STAT3, SLC7A11, and GPX4.
• STAT3 and SLC7A11 overexpression, or P53 inhibition, rescued OS cells from bavachin-induced ferroptosis.

Conclusions:

• Bavachin induces ferroptosis in osteosarcoma cells.
• The mechanism involves the STAT3/P53/SLC7A11 signaling axis.
• These findings highlight bavachin as a potential therapeutic agent for osteosarcoma through ferroptosis induction.