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Eicosapentaenoic acid‐induced apoptosis depends on acyl CoA‐synthetase
Author(s) -
Heimli Hilde,
Hollung Kristin,
Drevon Christian A.
Publication year - 2003
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-003-1059-z
Subject(s) - apoptosis , eicosapentaenoic acid , cell culture , cell growth , enzyme , biology , programmed cell death , biochemistry , microbiology and biotechnology , cell , chemistry , polyunsaturated fatty acid , fatty acid , genetics
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.