The tyrosine kinase inhibitor genistein increases basal cAMP and potentiates forskolin-induced cAMP accumulation in A549 human airway epithelial cells.
Genistein is often used as an inhibitor of tyrosine kinases. A less studied side effect of genistein is an inhibition of cyclic AMP-phosphodiesterase (cAMP-PDE) activity resulting in increased cAMP accumulation. The effect of genistein on intracellular cAMP-levels, basal and forskolin-induced, was studied in A549 human airway epithelial cells and compared with the unspecific PDE inhibitor, isobutylmethylxanthine (IBMX). It was shown that genistein (50 microM) increased basal cAMP and potentiated forskolin-induced cAMP accumulation to the same extent as IBMX (100 microM). Thus, the use of genistein in studies on signaling transductions may result in erroneous conclusions since increased cAMP may cause or contribute to the observed effects.
Burvall
Karin M
KM
National Institute for Working Life, Stockholm, Sweden. Karin.Burvall@niwl.se
Palmberg
Lena
L
Larsson
Kjell
K
D002460:Cell Line; D005576:Colforsin / Q000819:agonists* / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D005576:Colforsin; D019833:Genistein; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases