Enhancement of gap junctional communication by retinoids correlates with their ability to inhibit neoplastic transformation.
Retinoids that cause inhibition of methylcholanthrene-induced neoplastic transformation of C3H/10T1/2 cells enhance gap-junctional communication in carcinogen-initiated cells. Dose-response studies using retinoids of diverse structures and potency demonstrated a good correlation between these two events. Junctional permeability was enhanced by retinol and tetrahydrotetramethylnaphthalenyl propenylbenzoic acid (TTNPB) at concentrations from 10(-10) to 10(-6) M, and by retinoic acid between 10(-8) and 10(-6) M, the same concentrations that inhibited neoplastic transformation. Retinoic acid inhibited permeability at 10(-10) M, at which concentration transformation was enhanced. Retinoids caused similar alteration sin communication in parental 10T1/2 cells. Communication between initiated and 10T1/2 cells was not influenced by TTNPB. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibited junctional communication in initiated cells, in 10T1/2 cells and between these two cell lines. After repeated exposure of 10T1/2 cells to TPA only retinoid-enhanced communication was blocked; in contrast, basal communication became refractory. It is proposed that much of the chemopreventive action of retinoids can be explained by the enhanced junctional communication of growth regulatory signals.
Basic Science Program, Cancer Research Center, University of Hawaii, Honolulu 96813.
M Z
MZ
Hossain
L R
LR
Wilkens
P P
PP
Mehta
W
W
Loewenstein
J S
JS
Bertram
D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002478:Cells, Cultured; D007365:Intercellular Junctions / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008748:Methylcholanthrene / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D012176:Retinoids / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*; D014801:Vitamin A / Q000494:pharmacology*
D001565:Benzoates; D012176:Retinoids; D014801:Vitamin A; D008748:Methylcholanthrene; D014212:Tretinoin; C038864:4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid