Growth inhibition and apoptosis of RL human B lymphoma cells by vitamin E succinate and retinoic acid: role for transforming growth factor beta.
Vitamin E succinate (VES) and all-trans-retinoic acid (RA) were determined to be growth inhibitory for B lymphoma cells in vitro. RL, an Epstein-Barr virus-negative human cell line, was growth suppressed 87% with VES (5 micrograms/ml) and 58% with RA (10(-6) M); both agents blocked the cells in G1 of the cell cycle. The antiproliferative effect of VES seems to be independent of its potential antioxidant property because both fat- and water-soluble antioxidants were found to have no effect on RL cell proliferation. VES and RA increased IgM antibody concentrations in cell supernatants 5.8- and 9.9-fold, respectively. DNA fragmentation and flow cytometry studies showed VES- and RA-induced apoptosis in RL cells. VES- and RA-treated RL cells gradually underwent apoptosis over time with maximal induction occurring at days 6 and 5 of culture, respectively. A role for transforming growth factor beta in VES- and RA-mediated RL growth suppression is indicated by increased ligand and type II receptor protein expression. Furthermore, neutralizing antibodies to transforming growth factor beta 1 partially blocked the growth suppressive action of both VES and RA, thus suggesting that a TGF-beta autocrine negative loop was involved in VES and RA suppression of RL cell growth.
Turley
J M
JM
Laboratory of Leukocyte Biology, National Cancer Institute, Frederick, Maryland 21702, USA.
Funakoshi
S
S
Ruscetti
F W
FW
Kasper
J
J
Murphy
W J
WJ
Longo
D L
DL
Birchenall-Roberts
M C
MC
D000912:Antibodies, Neoplasm / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D024505:Tocopherols; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D000912:Antibodies, Neoplasm; D000975:Antioxidants; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D016212:Transforming Growth Factor beta; D014810:Vitamin E; D014212:Tretinoin; D024505:Tocopherols