PMID- 15145524
OWN - NLM
STAT- MEDLINE
DCOM- 20040722
LR  - 20131121
IS  - 0304-3835 (Print)
IS  - 0304-3835 (Linking)
VI  - 209
IP  - 1
DP  - 2004 Jun 8
TI  - Conjugated linoleic acid modulation of cell membrane in leukemia cells.
PG  - 87-103
AB  - This study compared the cellular uptake of pure conjugated linoleic acid isomers 
      (CLA(9c,11t) and CLA(9c,11c)) to linoleic acid (LA) and their effects on 
      polyunsaturated fatty acid (PUFA) synthesis, its metabolism into conjugated long 
      chain fatty acids (FAs) by desaturation and chain-elongation as well as cell 
      proliferation and the associated anticarcinogenic effects on various human 
      leukemia cell lines (K562, REH, CCRF-CEM and U937 cells). Furthermore, selective 
      effects of this individual isomers of CLA on desaturation steps involved in the 
      biosynthesis of PUFAs associated with cell growth were investigated. CLA isomers 
      supplemented in the culture medium was readily incorporated and esterified into 
      phospholipids (PLs) in the four cell lines in a concentration- and time-dependent 
      manner. The incorporation of the specific CLA isomers in PLs was similar to LA. 
      All four incubating leukemia cells (40 microM CLA for 48 h) showed very high 
      cellular CLA content in PLs (range: 32-63 g FA/100 g total phospholipid fatty 
      acid) affected by the nature of CLA and the cell type. Supplementation with CLA 
      or LA altered also cell membrane composition by n-6 PUFA synthesis. Accordingly, 
      CLA metabolism interferes with LA metabolism. We were able to show that CLA 
      isomers are converted by the leukemia cells of the same metabolic pathway into 
      conjugated diene fatty acids (CDFAs) as LA into non-conjugated PUFAs. In this 
      view, the gas chromatography-flame ionization detector detection of major CDFAs 
      (CD-18:3, CD-20:2 and CD-20:3) in cell membrane of CLA-treated cultures resulted 
      from successive Delta6-desaturation, elongation and Delta5-desaturation of CLA 
      isomers. However, in comparison to LA, relatively lower amounts of elongation 
      and/or desaturation metabolites were detected for CLA(9c,11t), and only minor 
      amounts or trace CDFAs were observed for CLA(9c,11c). Furthermore, CLA(9c,11t) 
      revealed only very low levels of CD-20:4 FA and no CLA(9c,11c)-conversion could 
      be detected. The metabolization of CLA indicated that CLA(9c,11c)<CLA(9c,11t) 
      were a poorer substrates in compared to LA for the 
      Delta5,6-desaturation/elongation in REH, CCRF-CEM and U937 cells or for the 
      Delta5-desaturation/elongation in the K562 cells. CLA(9c,11t) suppresses 
      Delta6-desaturation in CCRF-CEM, REH, and U937 cells (43.5, 54.6 and 58.8% 
      Delta6-inhibition, respectively) and as well Delta9-desaturation in all four cell 
      lines (Delta9-inhibition; 47.1, 33.9, 29.8 and 25.9% for CCRF-CEM, REH, K562 and 
      U937 cells, respectively). However, CLA(9c,11c) does not inhibit or only slightly 
      affected these desaturations. CLA(9c,11t) isomer was found as an 
      Delta6-desaturase inhibitor with a dose-dependent relationship between inhibition 
      of Delta6-desaturase activity and decreases in cell growth. The growth inhibitory 
      effects of CLA (with 30-120 microM) on leukemia cells were dependent upon the 
      type and concentration of CLA isomers present. CLA-supplemented cells with low 
      concentrations (<60 microM) were not sufficient to impair cell proliferation. 
      Nevertheless, higher amounts of CLAs (>60 microM) had the CLA type dependent 
      antiproliferative effects. Thus, the 9cis,11trans- and the 9cis,11cis-CLA isomers 
      regulate cell growth and survival in different leukemia cell types through their 
      existence alone and/or by their inhibitory effects of desaturase activity.
FAU - Agatha, Gerhard
AU  - Agatha G
AD  - Friedrich-Schiller-University of Jena, Children's Hospital, Department of 
      Pediatrics, Endocrinology and Metabolism, Kochstrasse 2, D-07745 Jena, Germany. 
      gerhard.agatha@med.uni-jena.de
FAU - Voigt, Astrid
AU  - Voigt A
FAU - Kauf, Eberhard
AU  - Kauf E
FAU - Zintl, Felix
AU  - Zintl F
LA  - eng
PT  - Journal Article
PL  - Ireland
TA  - Cancer Lett
JT  - Cancer letters
JID - 7600053
RN  - 0 (Culture Media)
RN  - 0 (Fatty Acids)
RN  - 0 (Fatty Acids, Unsaturated)
RN  - 0 (Linoleic Acids, Conjugated)
RN  - 9KJL21T0QJ (Linoleic Acid)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cell Membrane/*drug effects
MH  - Cell Survival
MH  - Chromatography, Gas
MH  - Culture Media/pharmacology
MH  - Fatty Acids/metabolism
MH  - Fatty Acids, Unsaturated/metabolism
MH  - Humans
MH  - K562 Cells
MH  - Leukemia/*drug therapy
MH  - Linoleic Acid/pharmacology
MH  - Linoleic Acids, Conjugated/*pharmacology
MH  - Models, Biological
MH  - Oxygen/metabolism
MH  - Time Factors
MH  - U937 Cells
EDAT- 2004/05/18 05:00
MHDA- 2004/07/23 05:00
CRDT- 2004/05/18 05:00
PHST- 2003/08/20 00:00 [received]
PHST- 2003/11/20 00:00 [revised]
PHST- 2003/11/26 00:00 [accepted]
PHST- 2004/05/18 05:00 [pubmed]
PHST- 2004/07/23 05:00 [medline]
PHST- 2004/05/18 05:00 [entrez]
AID - S0304383503008127 [pii]
AID - 10.1016/j.canlet.2003.11.022 [doi]
PST - ppublish
SO  - Cancer Lett. 2004 Jun 8;209(1):87-103. doi: 10.1016/j.canlet.2003.11.022.