Suppression of Lipogenesis via Reactive Oxygen Species-AMPK Signaling for Treating Malignant and Proliferative...

Area of Science:

• Biochemistry
• Oncology
• Immunology

Background:

• Systemic diseases share common characteristics.
• Malignant and proliferative diseases, such as gefitinib-resistant nonsmall-cell lung cancer (G-R NSCLC) and rheumatoid arthritis (RA), exhibit high lipogenic activity and sterol regulatory element-binding protein 1 (SREBP1) expression.
• Synovial fibroblasts from RA patients (RASFs) and G-R NSCLC cells show similar metabolic profiles.

Purpose of the Study:

• To investigate the feasibility of targeting common pathological metabolism to inhibit the progression of malignant and proliferative diseases.
• To explore the therapeutic potential of berberine (BBR) in G-R NSCLC and RA models.

Main Methods:

• Investigated lipogenic activity and SREBP1 expression in G-R NSCLC cells and RASFs.
• Examined the effect of BBR on cellular lipogenesis, proliferation, and the reactive oxygen species (ROS)/AMPK pathway.
• Assessed the in vivo efficacy of BBR in mouse tumor xenograft and rat adjuvant-induced arthritis models.

Main Results:

• Berberine (BBR) selectively inhibited the growth of G-R NSCLC cells and RASFs by suppressing lipogenesis.
• BBR induced mitochondrial dysfunction and activated the ROS/AMPK pathway, leading to reduced cell proliferation.
• In vivo studies demonstrated that BBR significantly inhibited tumor xenograft growth and slowed the progression of arthritis.

Conclusions:

• Targeting the ROS/AMPK/lipogenesis signaling pathway offers a novel therapeutic strategy for malignancies and proliferative diseases.
• BBR demonstrates therapeutic potential for treating G-R NSCLC and RA by selectively inhibiting pathological metabolism.
• This study provides a new avenue for developing treatments for complex systemic diseases.