Idebenone Exerts anti-Triple Negative Breast Cancer Effects via Dual Signaling Pathways of GADD45 and AMPK

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Triple-negative breast cancer (TNBC) lacks targeted therapies, necessitating novel treatment strategies.
• Idebenone, a mitochondrial regulator, has demonstrated anti-cancer effects in other tumor types, but its role in TNBC is unexplored.

Purpose of the Study:

• To investigate the therapeutic potential of Idebenone against triple-negative breast cancer (TNBC).
• To elucidate the underlying molecular mechanisms of Idebenone's anti-cancer activity in TNBC.

Main Methods:

• Utilized TNBC cell lines and Xenograft mouse models for in vitro and in vivo assessments.
• Employed cell viability, invasion, cell cycle, apoptosis, mitochondrial membrane potential assays, immunofluorescence, and transcriptome sequencing.
• Investigated the GADD45/CyclinB/CDK1 and AMPK/mTOR signaling pathways.

Main Results:

• Idebenone significantly inhibited TNBC cell proliferation, colony formation, migration, and invasion.
• Idebenone induced G2/M phase cell cycle arrest and apoptosis, while disrupting mitochondrial membrane potential.
• Idebenone promoted autophagy via the AMPK/mTOR pathway and inhibited TNBC tumor growth in vivo.

Conclusions:

• Idebenone exhibits significant anti-cancer effects against TNBC through the induction of autophagy and apoptosis.
• Idebenone demonstrates potential as a novel therapeutic agent for triple-negative breast cancer.
• The GADD45/CyclinB/CDK1 and AMPK/mTOR pathways are implicated in Idebenone's mechanism of action in TNBC.