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Saturated Oxo Fatty Acids (SOFAs): A Previously Unrecognized Class of Endogenous Bioactive Lipids Exhibiting a Cell
Charikleia S Batsika1, Christiana Mantzourani1, Dimitrios Gkikas2,3
1Center of Excellence for Drug Design and Discovery, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 15771, Greece.
Abstract:
The discovery of novel bioactive lipids that promote human health is of great importance. Combining "suspect" and targeted lipidomic liquid chromatography-high-resolution mass spectrometry (LC-HRMS) approaches, a previously unrecognized class of oxidized fatty acids, the saturated oxo fatty acids (SOFAs), which carry the oxo functionality at various positions of the long chain, was identified in human plasma. A library of SOFAs was constructed, applying a simple green photochemical hydroacylation reaction as the key synthetic step. The synthesized SOFAs were studied for their ability to inhibit in vitro the cell growth of three human cancer cell lines. Four oxostearic acids (OSAs) were identified to inhibit the cell growth of human lung carcinoma A549 cells. 6OSA and 7OSA exhibited the highest cell growth inhibitory potency, suppressing the expression of both STAT3 and c-myc, which are critical regulators of cell growth and proliferation. Thus, naturally occurring SOFAs may play a role in the protection of human health.
Insights
Researchers discovered saturated oxo fatty acids (SOFAs) in human plasma. These novel lipids, specifically certain oxostearic acids (OSAs), show potential in inhibiting cancer cell growth by regulating key growth factors.
Area of Science:
- Lipidomics
- Biochemistry
- Cancer Biology
Background:
- The identification of novel bioactive lipids is crucial for understanding human health.
- Oxidized fatty acids represent a class of lipids with significant biological implications.
- Existing lipidomic techniques require enhancement for comprehensive analysis.
Purpose of the Study:
- To discover and characterize previously unrecognized classes of oxidized fatty acids in human plasma.
- To synthesize identified oxidized fatty acids for further biological evaluation.
- To investigate the potential anti-cancer properties of these novel lipids.
Main Methods:
- Utilized a combination of "suspect" and targeted lipidomic liquid chromatography-high-resolution mass spectrometry (LC-HRMS) for lipid identification.
- Synthesized a library of saturated oxo fatty acids (SOFAs) using a green photochemical hydroacylation reaction.
- Assessed the in vitro effects of synthesized SOFAs on the cell growth of human cancer cell lines.
Main Results:
- Identified a novel class of oxidized fatty acids, saturated oxo fatty acids (SOFAs), in human plasma.
- Synthesized a library of SOFAs, including four oxostearic acids (OSAs).
- Demonstrated that 6OSA and 7OSA significantly inhibit the cell growth of human lung carcinoma A549 cells by suppressing STAT3 and c-myc expression.
Conclusions:
- Naturally occurring SOFAs represent a newly discovered class of bioactive lipids.
- Specific SOFAs, like 6OSA and 7OSA, possess potent anti-cancer properties.
- SOFAs may play a significant role in the body's natural defense mechanisms and overall health protection.
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