Growth inhibition and apoptosis of RL human B lymphoma cells by vitamin E succinate and retinoic acid: role for transforming growth factor beta

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Published on Tuesday, 16 July 2013

Abstract

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.

 

 

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See also:

- All-Trans-Retinoic Acid (ATRA - analogues and/or derivatives);

- Cyclophosphamide plus Somatostatin, Bromocriptin, Retinoids, Melatonin and ACTH in the Treatment of Low-grade Non-Hodgkin’s Lymphomas at Advanced Stage: Results of a Phase II Trial;

- Relapse of High-Grade Non-Hodgkin’s Lymphoma After Autologous Stem Cell Transplantation: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Melatonin, Retinoids, and ACTH;

- Low-grade Non-Hodgkin Lymphoma at Advanced Stage: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Retinoids, and Melatonin;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 55 cases of Lymphomas.