Document Detail

The effect of leukotrienes B and selected HETEs on the proliferation of colon cancer cells.
MedLine Citation:
PMID:  8679690     Owner:  NLM     Status:  MEDLINE    
Eicosanoids have been implicated in colon carcinogenesis, but very little is known on the potential role of leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs) in this process; such compounds are produced by colonocytes and tumor infiltrating leukocytes. We studied the effect of LTB4, LTB4 methyl ester, LTB5, 12(R)-HETE, 12(S)-HETE and 15(S)-HETE (10(-10), 10(-8), 10(-6) M) on the proliferation rate, the cell cycle distribution, and the rate of apoptosis in HT-29 and HCT-15 human colon carcinoma cells. Our data show that LTB4, a lipoxygenase product, increased the proliferation rate of both cell lines in a time- and concentration-dependent manner. In HT-29 cells the concentration-response curve was bell-shaped (maximal effect at 10(-8) M). The proliferative effects of LTB4 in HT-29 cells were inhibited by SC-41930, a competitive antagonist of LTB4, suggesting the existence of an LTB4 receptor in epithelial cells. The methyl ester of LTB4 stimulated the proliferation of these cells, but LTB5, an isomer of LTB4 derived from eicosapentaenoic acid, did not. Of the HETEs, only 12(R)-HETE, a P-450 product, stimulated the proliferation of both cell lines; the other HETEs, all lipoxygenase products, failed to affect the proliferation of these cells. None of these eicosanoids had any effect on cell cycle distribution or apoptosis in either cell line. Taken together with our previous data showing that PGs stimulate colon cancer cell proliferation (Qiao et al. (1995) Biochim. Biophys. Acta 1258, 215-223), these findings indicate that arachidonic acid products synthesized via at least three different pathways (cyclooxygenase, lipoxygenase, P-450) may not be able to modulate the growth of colon cancer, and suggest a potential role in human colon carcinogenesis for LTB4 and 12(R)-HETE.
C Bortuzzo; R Hanif; K Kashfi; L Staiano-Coico; S J Shiff; B Rigas
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1300     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  1996 May 
Date Detail:
Created Date:  1996-08-16     Completed Date:  1996-08-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  240-6     Citation Subset:  IM    
Division of Digestive Diseases, New York Hospital Medical Center of Queens, NY, USA.
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MeSH Terms
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
Anti-Inflammatory Agents, Non-Steroidal / pharmacology
Apoptosis / drug effects
Benzopyrans / pharmacology
Cell Division / drug effects
Colonic Neoplasms / pathology*
Eicosanoids / pharmacology*
Flow Cytometry
Hydroxyeicosatetraenoic Acids / pharmacology
Interphase / drug effects
Leukotriene B4 / antagonists & inhibitors,  pharmacology*
Mitosis / drug effects
Receptors, Leukotriene / drug effects
S Phase / drug effects
Tumor Cells, Cultured
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Benzopyrans; 0/Eicosanoids; 0/Hydroxyeicosatetraenoic Acids; 0/Receptors, Leukotriene; 120072-59-5/SC 41930; 59985-28-3/12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; 71160-24-2/Leukotriene B4; 73945-47-8/15-hydroxy-5,8,11,13-eicosatetraenoic acid

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