Calcium-independent phospholipase A2 through arachidonic acid mobilization is involved in Caco-2 cell growth.
Several studies indicate that phospholipase A(2) (PLA(2)) expression and/or activation account for the high levels of arachidonic acid (AA) detected in cancer and, together with the elevated expression of cyclooxygenase-2, lead to cell proliferation and tumor formation. Using Caco-2 cells, a human colorectal carcinoma cell, we studied the role of high-molecular-weight PLA(2)s, cytosolic PLA(2) (cPLA(2)), and calcium-independent PLA(2) (iPLA(2)) in the AA cascade and in cell growth. Treatment with an antisense oligonucleotide against cPLA(2)alpha decreased [(3)H]AA release induced by ionophore A23187 or by a phorbol ester but did not affect the release of [(3)H]AA, [(3)H]thymidine incorporation, or Caco-2 growth induced by fetal calf serum (FCS). However, these parameters were significantly modified by iPLA(2) inhibitors and by an antisense oligonucleotide against iPLA(2)beta. Our results show that iPLA(2) was involved in AA release and the subsequent prostaglandin production induced by serum. Moreover, these data indicate that iPLA(2) may be involved in the signaling pathways involved in the control of Caco-2 proliferation.
Sanchez
Teresa
T
Department of Physiology, Faculty of Pharmacy, Barcelona University, Barcelona, Spain.
Moreno
Juan J
JJ
D016718:Arachidonic Acid / Q000378:metabolism*; D018938:Caco-2 Cells; D002277:Carcinoma / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D015232:Dinoprostone / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054513:Group IV Phospholipases A2; D054522:Group VI Phospholipases A2; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D054467:Phospholipases A2
D004791:Enzyme Inhibitors; D016376:Oligonucleotides, Antisense; D016718:Arachidonic Acid; D010741:Phospholipases A; D054513:Group IV Phospholipases A2; D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human; D054467:Phospholipases A2; D015232:Dinoprostone