Fumonisin B1 influenced the effects of arachidonic acid, prostaglandins E2 and A2 on cell cycle progression, apoptosis induction, tyrosine- and CDC2-kinase activity in oesophageal cancer cells.
In a previous study, we showed that, of a group of lipids including arachidonic acid (AA), prostaglandins E2 (PGE2) and A2 (PGA2), PGA2 had the most marked effect on the inhibition of cell growth, activation of tyrosine kinase activity, lowering of the number of G1-phase cells, and induction of p53 levels in oesophageal carcinoma (WHCO3) cells. No significant effects by the three lipids were seen in normal monkey kidney cells. In the present study, the effects of the inhibitor of ceramide synthesis, fumonisin B1 (FB1), a metabolite of Fusarium verticillioides (= F. moniliforme) which is implicated in the high incidence of oesophageal cancer, were determined on AA, PGE2 and PGA2 WHCO3 treated cells. In the presence of FB1, the lipid-enhanced tyrosine kinase activity was lowered. Flow cytometric and morphological studies showed that FB1 lowered the marked apoptosis induced by especially PGA2. FB1, however, in combination with AA, PGE2 or PGA2 increased the number of G2/M cells. AA>PGE2>PGA2 alone decreased CDC2-kinase activity, but, in the presence of FB1, CDC2-kinase activity was significantly increased. The PGA2- and AA-induced p53 levels were lowered in the presence of FB1. We concluded that FB1 diminished the cytotoxic effects of the lipids on oesophageal tumour cells.
Seegers
J C
JC
Department of Physiology, Faculty of Medicine, University of Pretoria, South Africa. jseegers@medic.up.ac.za
Joubert
A M
AM
Panzer
A
A
Lottering
M L
ML
Jordan
C A
CA
Joubert
F
F
Maree
J L
JL
Bianchi
P
P
de Kock
M
M
Gelderblom
W C
WC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016718:Arachidonic Acid / Q000494:pharmacology*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002264:Carboxylic Acids / Q000494:pharmacology*; D002274:Carcinogens, Environmental / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D015232:Dinoprostone / Q000494:pharmacology; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000473:pathology*; D037341:Fumonisins; D006801:Humans; D011453:Prostaglandins / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D002264:Carboxylic Acids; D002274:Carcinogens, Environmental; D037341:Fumonisins; D011453:Prostaglandins; D016159:Tumor Suppressor Protein p53; D016718:Arachidonic Acid; C056933:fumonisin B1; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D016203:CDC2 Protein Kinase; D015232:Dinoprostone