Modification of the expression of adenosine 3',5'-cyclic monophosphate-induced differentiated functions in neuroblastoma cells by beta-carotene and D-alpha-tocopheryl succinate.
OBJECTIVE
The role of beta-carotene and vitamin E in modifying the effect of cell differentiating agent has not been studied. This study has investigated the effects of beta-carotene and d-alpha-tocopheryl succinate (alpha-TS) on adenosine 3',5'-cyclic monophosphate (cAMP) induced differentiated functions in murine neuroblastoma cells (NBP2) in culture.


METHODS
Prostaglandin E1 (PGE1), a stimulator of adenylate cyclase, and 4-(3-butoxy-4-methoxy-benzyl)-2-imidazolidinone (R020-1724), an inhibitor of cyclic nucleotide phosphodiesterase, were used to induce differentiation in NB cells.


RESULTS
Both beta-carotene and alpha-TS markedly enhanced the level of morphologic differentiation (neurite formation) induced by both PGE1 and R020-1724. However, beta-carotene and alpha-TS by themselves were ineffective. These vitamins increased tyrosine hydroxylase (TH) activity. However, beta-carotene did not significantly affect PGE1- and R020-1724-stimulated rise in TH activity. alpha-TS at a higher concentration inhibited PGE1- and R020-1724-stimulated increase in TH activity. None of the above treatments affected basal choline acetyltransferase (ChAT) activity. beta-carotene and alpha-TS caused a transient increase in cAMP level, and they also enhanced the effect of PGE1 and R020-1724 on cAMP level in a transient manner.


CONCLUSIONS
These results suggest that beta-carotene and alpha-TS modify the effects of cAMP stimulating agents on differentiation of NB cells in culture.
Prasad
K N
KN
Department of Radiology, School of Medicine, University of Colorado Health Sciences Center, Denver 80262-0276.
Kentroti
S
S
Edwards-Prasad
J
J
Vernadakis
A
A
Imam
M
M
Carvalho
E
E
Kumar
S
S
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D002338:Carotenoids / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D024505:Tocopherols; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology; D019207:beta Carotene
D019207:beta Carotene; D014810:Vitamin E; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D002338:Carotenoids; D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase; D000527:Alprostadil; D024505:Tocopherols