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.
Hossain
M Z
MZ
Basic Science Program, Cancer Research Center, University of Hawaii, Honolulu 96813.
Wilkens
L R
LR
Mehta
P P
PP
Loewenstein
W
W
Bertram
J S
JS
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