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Suppression of Lipogenesis via Reactive Oxygen Species-AMPK Signaling for Treating Malignant and Proliferative Diseases.
- Source :
-
Antioxidants & redox signaling [Antioxid Redox Signal] 2018 Feb 10; Vol. 28 (5), pp. 339-357. Date of Electronic Publication: 2017 Aug 04. - Publication Year :
- 2018
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Abstract
- Aims: Systemic diseases often have common characteristics. The aim of this study was to investigate the feasibility of targeting common pathological metabolism to inhibit the progression of malignant and proliferative diseases.<br />Results: Gefitinib-resistant (G-R) nonsmall-cell lung cancer (NSCLC) and rheumatoid arthritis (RA) were studied as conditions representative of malignant and proliferative diseases, respectively. Strong lipogenic activity and high expression of sterol regulatory element-binding protein 1 (SREBP1) were found in both G-R NSCLC cells and synovial fibroblasts from RA patients (RASFs). Berberine (BBR), an effective suppressor of SREBP1 and lipogenesis regulated through reactive oxygen species (ROS)/AMPK pathway, selectively inhibited the growth of G-R NSCLC cells and RASFs but not that of normal cells. It effectively caused mitochondrial dysfunction, activated ROS/AMPK pathway, and finally suppressed cellular lipogenesis and cell proliferation. Addition of ROS blocker, AMPK inhibitor, and palmitic acid significantly reduced the effect of BBR. In an in vivo study, treatment of BBR led to significant inhibition of mouse tumor xenograft growth and remarkably slowed down the development of adjuvant-induced arthritis in rats. Innovation and Conclusion: Targeting ROS/AMPK/lipogenesis signaling pathway selectively inhibited the growth of G-R NSCLC cells and the progress of RASFs in vitro and in vivo, which provides a new avenue for treating malignancies and proliferative diseases. Antioxid. Redox Signal. 28, 339-357.
- Subjects :
- Arthritis, Rheumatoid genetics
Arthritis, Rheumatoid metabolism
Arthritis, Rheumatoid pathology
Berberine administration & dosage
Carcinoma, Non-Small-Cell Lung genetics
Carcinoma, Non-Small-Cell Lung metabolism
Carcinoma, Non-Small-Cell Lung pathology
Cell Line, Tumor
Cell Proliferation drug effects
Drug Resistance, Neoplasm genetics
Fibroblasts drug effects
Fibroblasts pathology
Gefitinib
Gene Expression Regulation drug effects
Humans
Oxidation-Reduction
Quinazolines administration & dosage
Quinazolines adverse effects
Reactive Oxygen Species metabolism
Signal Transduction drug effects
Synovial Fluid drug effects
Synovial Fluid metabolism
AMP-Activated Protein Kinases genetics
Arthritis, Rheumatoid drug therapy
Carcinoma, Non-Small-Cell Lung drug therapy
Lipogenesis genetics
Sterol Regulatory Element Binding Protein 1 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1557-7716
- Volume :
- 28
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Antioxidants & redox signaling
- Publication Type :
- Academic Journal
- Accession number :
- 28665143
- Full Text :
- https://doi.org/10.1089/ars.2017.7090