Artesunate-binding FABP5 promotes apoptosis in lung cancer cells via the PPARγ-SCD pathway

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Artesunate shows promise for lung cancer treatment, but its molecular target remains unidentified.
• Understanding artesunate's mechanism of action is crucial for developing effective lung cancer therapies.

Purpose of the Study:

• To identify the specific protein target of artesunate in lung cancer.
• To elucidate the molecular pathway through which artesunate induces apoptosis in lung cancer cells.

Main Methods:

• Molecular docking simulations were employed to predict binding sites between artesunate and Fatty acid binding protein 5 (FABP5).
• Cellular thermal shift assay (CETSA) was used to validate the interaction and assess protein stability upon artesunate treatment.
• Gene expression analysis was performed to evaluate the impact on lipid metabolism and related transcription factors.

Main Results:

• Molecular docking identified FABP5 as a potential binding partner for artesunate.
• CETSA confirmed that artesunate enhances the stability of the FABP5 protein.
• Artesunate treatment led to the inhibition of the lipid metabolism gene SCD and its regulating transcription factor PPARγ, ultimately promoting apoptosis in lung cancer cells.

Conclusions:

• The study identifies FABP5 as the direct protein target of artesunate in lung cancer.
• Artesunate induces apoptosis in lung cancer cells through the FABP5-PPARγ-SCD signaling pathway.
• This pathway presents a promising therapeutic strategy for lung cancer treatment.