Trifluoperazine activates AMPK / mTOR / ULK1 signaling pathway to induce mitophagy in osteosarcoma cells

Area of Science:

• Oncology
• Pharmacology
• Cell Biology

Background:

• Osteosarcoma is a common primary bone cancer.
• Trifluoperazine, an antipsychotic, exhibits anti-tumor properties in various cancers.
• The specific effects of trifluoperazine on osteosarcoma remain largely unexplored.

Purpose of the Study:

• To investigate the anti-cancer mechanism of trifluoperazine in osteosarcoma cells.
• To elucidate the role of reactive oxygen species (ROS) and mitophagy in trifluoperazine's action.
• To identify the signaling pathways involved in trifluoperazine-induced mitophagy.

Main Methods:

• Cell proliferation assays on osteosarcoma cell lines (143B and U2-OS).
• Measurement of reactive oxygen species (ROS) accumulation and assessment of mitochondrial damage.
• RNA sequencing (RNA-seq) to analyze gene expression changes.
• Investigation of the AMPK/mTOR/ULK1 signaling pathway and the effect of Compound C (AMPK inhibitor).

Main Results:

• Trifluoperazine demonstrated dose-dependent inhibition of osteosarcoma cell proliferation.
• The drug induced significant ROS accumulation, leading to mitochondrial damage.
• Trifluoperazine treatment resulted in increased mitophagy in osteosarcoma cells.
• RNA-seq data revealed the involvement of the AMPK/mTOR/ULK1 pathway in trifluoperazine-mediated mitophagy.
• The AMPK inhibitor Compound C suppressed trifluoperazine-induced mitophagy.

Conclusions:

• Trifluoperazine exhibits anti-proliferative effects on osteosarcoma cells.
• Trifluoperazine induces osteosarcoma cell death through ROS-mediated mitochondrial damage and mitophagy.
• The AMPK/mTOR/ULK1 signaling pathway is a key mechanism underlying trifluoperazine-induced mitophagy in osteosarcoma.