Docosahexaenoic acid suppresses arachidonic acid-induced proliferation of LS-174T human colon carcinoma cells.
OBJECTIVE
To investigate the impact of arachidonic acid (AA) and docosahexaenoic acid (DHA) and their combination on colon cancer cell growth.


METHODS
The LS-174T colon cancer cell line was used to study the role of the prostaglandin precursor AA and the omega-3 polyunsaturated fatty acid DHA on cell growth. Cell viability was assessed in XTT assays. For analysis of cell cycle and cell death, flow cytometry and DAPI staining were applied. Expression of cyclooxygenase-2 (COX-2), p21 and bcl-2 in cells incubated with AA or DHA was examined by real-time RT-PCR. Prostaglandin E(2) (PGE(2)) generation in the presence of AA and DHA was measured using a PGE(2)-ELISA.


RESULTS
AA increased cell growth, whereas DHA reduced viability of LS 174T cells in a time- and dose-dependent manner. Furthermore, DHA down- regulated mRNA of bcl-2 and up-regulated p21. Interestingly, DHA was able to suppress AA-induced cell proliferation and significantly lowered AA-derived PGE(2) formation. DHA also down-regulated COX-2 expression. In addition to the effect on PGE(2) formation, DHA directly reduced PGE(2)-induced cell proliferation in a dose-dependent manner.


CONCLUSIONS
These results suggest that DHA can inhibit the pro-proliferative effect of abundant AA or PGE(2).
Habbel
Piet
P
Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, United States.
Weylandt
Karsten H
KH
Lichopoj
Katja
K
Nowak
Johannes
J
Purschke
Martin
M
Wang
Jing-Dong
JD
He
Cheng-Wei
CW
Baumgart
Daniel C
DC
Kang
Jing X
JX
D016718:Arachidonic Acid / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000235:genetics; D015232:Dinoprostone / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D051546:Cyclooxygenase 2; D015232:Dinoprostone