AH6809 antagonizes non-small cell lung cancer prostaglandin receptors.
The effects of prostaglandin (PG)E2 on lung cancer cells were investigated. 3H-PGE2 bound with high affinity to membranes derived from small cell lung cancer (SCLC) and non-SCLC (NSCLC) cell lines. Using NSCLC NCI-H1299 membranes, specific 3H-PGE2 binding to NCI-H1299 membranes was inhibited with moderate affinity by PGE2, PGE1, PGF2alpha and 6-isopropoxy-9-xanthone-2-carboxylic acid (AH6809) but not PGD2, LTB4 or 5-HETE. By RT-PCR, EP2 receptor PCR products were detected in extracts derived from lung cancer cells. PGE2 caused cAMP elevation in a concentration-dependent manner using NCI-H1299 cells and the increase in cAMP caused by PGE2 was antagonized by AH6809. PGE2 had no effect on cytosolic Ca2+ but PGE2 caused increased c-fos mRNA in NCI-H1299 cells. AH6809 inhibited the proliferation of NCI-H1299 cells using MTT and clonogenic assays. These results indicate that functional PG receptors are present on NSCLC cells which are antagonized by AH6809.
Casibang
Marchessini
M
Cell and Cancer Biology Department, Medicine Branch, NCI, Bldg. KWC, Rm. 300, 9610 Medical Center Drive, Rockville, MD 20850, USA.
Moody
Terry W
TW
D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects*; D002462:Cell Membrane / Q000502:physiology; D003114:Colony-Forming Units Assay; D000242:Cyclic AMP / Q000378:metabolism; D003593:Cytoplasm; D017931:DNA Primers / Q000737:chemistry; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014966:Xanthenes / Q000494:pharmacology*; D044004:Xanthones
D017931:DNA Primers; D011448:Prostaglandin Antagonists; D012333:RNA, Messenger; D011982:Receptors, Prostaglandin; D014966:Xanthenes; D044004:Xanthones; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; D000242:Cyclic AMP; D015232:Dinoprostone; D002118:Calcium