Effect of prostaglandin E-2 on the proliferation, Ca2+ mobilization and cAMP in HT-29 human colon adenocarcinoma cells

Several lines of evidence suggest that non-steroidal antiinflammatory drugs (NSAIDs) have anticarcinogenic effects. The causal relationship linking th e preventive effect of NSAIDs on colon cancer and the inhibition of prostag landin synthesis is questioned by the contrasting results obtained by many laboratories. The experiments reported in this paper demonstrate that prost aglandin E-2 (PGE(2)) did not stimulate the proliferation in HT-29 human co lon adenocarcinoma cells under several experimental conditions. Moreover, P GE(2) and 17-phenyl trinor prostaglandin E-2 (a specific agonist of EP1 rec eptors) did not increase intracellular Ca2+ concentration. Finally, PGE(2) did not affect the intracellular cAMP and did not reduce the isoproterenol dependent increase in cAMP. These results indicate that in HT-29 cells: (1) proliferation is not directly sensitive to PGE(2); and (2) PGE(2) does not stimulate a signal transduction pathway leading to intracellular increase in cAMP or Ca2+ mobilization. Therefore, other cell lines should be used to assess the direct role played by prostanoids in promoting cell proliferati on in colon cancer. (C) 2000 Elsevier Science Ireland Ltd. All rights reser ved.