Effect of prostaglandin E(2) on the proliferation, Ca(2+) 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 the preventive effect of NSAIDs on colon cancer and the inhibition of prostaglandin synthesis is questioned by the contrasting results obtained by many laboratories. The experiments reported in this paper demonstrate that prostaglandin E(2) (PGE(2)) did not stimulate the proliferation in HT-29 human colon adenocarcinoma cells under several experimental conditions. Moreover, PGE(2) and 17-phenyl trinor prostaglandin E(2) (a specific agonist of EP1 receptors) did not increase intracellular Ca(2+) 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 Ca(2+) mobilization. Therefore, other cell lines should be used to assess the direct role played by prostanoids in promoting cell proliferation in colon cancer.
Cassano
G
G
Dipartimento di Fisiologia Generale ed Ambientale, Università di Bari, Via Amendola 165/A, 70126, Bari, Italy.
Gasparre
G
G
Susca
F
F
Lippe
C
C
Guanti
G
G
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001839:Bombesin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D015398:Signal Transduction; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000242:Cyclic AMP; D015232:Dinoprostone; D001839:Bombesin; D002118:Calcium; D007213:Indomethacin