Abstract
Marine n−3 FA are known to inhibit proliferation or induce cell death in several cancer cell lines. We have previously reported that EPA promotes apoptosis in the lymphoma cell line Ramos, whereas the U-698 cell line is insensitive to EPA. Furthermore, acyl-CoA synthetase (ACS) is expressed to a higher extent in Ramos cells compared to U-698 cells. To investigate the importance of ACS in EPA-induced apoptosis, we incubated Ramos cells with triacsin C, an inhibitor of ACS. This caused a 70% reduction in the amount of cell-associated EPA and diminished activation of EPA. In addition, triacsin C caused a 90% reduction in EPA-induced apoptosis. Several different approaches were tried to overexpress ACS4 in EPA-insensitive lymphoma cell lines, but we did not obtain viable cells with high expression of acyl-CoA activation. However, we show that overexpression of ACS4 in the more robust COS-1 cells caused up to a fivefold increase in activation of EPA and a 67% increase in the amount of cell-associated radiolabeled EPA. Furthermore, we observed 28% elevated cellular level of TAG in EPA-incubated COS-1 cells overexpressing ACS4. The present study provides new information about ACS as an important enzyme for EPA-induced apoptosis in Ramos cells. Our data offer a potential mechanism that may explain the effect of dietary marine n−3 PUFA on growth of certain malignant cells.
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Abbreviations
- AA:
-
arachidonic acid
- ACS:
-
acyl-CoA synthetase
- FABP:
-
fatty acid-binding protein
- HO342:
-
Hoechst 33342
- OA:
-
oleic acid
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Heimli, H., Hollung, K. & Drevon, C.A. Eicosapentaenoic acid-induced apoptosis depends on acyl CoA-synthetase. Lipids 38, 263–268 (2003). https://doi.org/10.1007/s11745-003-1059-z
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DOI: https://doi.org/10.1007/s11745-003-1059-z