Deferoxamine suppresses esophageal squamous cell carcinoma cell growth via ERK1/2 mediated mitochondrial dysfunction

Area of Science:

• Oncology
• Molecular Biology
• Cellular Signaling

Background:

• Deferoxamine (DFO) is known to affect various cancer types, but its impact on esophageal squamous cell carcinoma (ESCC) is not well understood.
• Esophageal squamous cell carcinoma (ESCC) remains a significant global health challenge with limited therapeutic options.

Purpose of the Study:

• To investigate the anti-tumorigenic effects of Deferoxamine (DFO) on esophageal squamous cell carcinoma (ESCC) cells.
• To elucidate the underlying molecular mechanisms by which DFO exerts its anti-cancer activity in ESCC.

Main Methods:

• Cell proliferation assays, cell cycle analysis, and apoptosis assays were performed on DFO-treated ESCC cells.
• Reactive oxygen species (ROS) levels, ERK1/2 signaling pathway activation, mitochondrial respiration, and aerobic glycolysis were assessed.
• The role of ROS, ERK1/2, and c-Myc in DFO's anti-tumorigenic effects was evaluated using specific inhibitors and scavengers.

Main Results:

• DFO treatment significantly inhibited ESCC cell proliferation, induced cell cycle arrest, and promoted apoptosis.
• DFO activated ROS-dependent ERK1/2 signaling, which suppressed mitochondrial respiration and aerobic glycolysis, reducing ATP production.
• DFO-induced ERK1/2 activation was partially translocated to mitochondria, and decreased c-Myc expression inhibited cell migration.

Conclusions:

• DFO demonstrates potent anti-neoplastic activity against ESCC by activating ERK1/2 and downregulating c-Myc.
• The mechanism involves perturbing mitochondrial homeostasis and promoting apoptosis, offering a novel therapeutic strategy for ESCC.
• Targeting the ERK1/2 pathway and c-Myc may be crucial for DFO's efficacy in esophageal cancer treatment.