9342185

pubmed:Citation

10

Retinoids have been shown to modulate cell growth and differentiation in a variety of human tumor cell types, but their effects on B-cell non-Hodgkin's lymphomas (NHL-B) have not been explored. In this study, all-trans retinoic acid (ATRA) in the free form and liposome-encapsulated form (L-ATRA) were used to determine effects on fresh NHL-B patient cells as well as cell lines recently established from both HIV-negative and -positive NHL-B patient biopsies. Both ATRA and L-ATRA were found to inhibit cell proliferation in NHL-B cells. However, L-ATRA was found to be superior to free ATRA in inhibiting cell proliferation of NHL-B cells and resulted in greater than 90% cell growth inhibition in a dose-dependent manner. In addition, L-ATRA also induced high levels of apoptosis in NHL-B cells in vitro. To delineate the apoptotic pathways involved, the expression of the apoptosis suppressor oncogene bcl-2 was evaluated in different NHL-B cells with and without the t(14;18) chromosomal translocation. After L-ATRA exposure, more than a 50% reduction in the expression of bcl-2 protein was observed. bcl-2 message levels were also down-regulated in the L-ATRA-sensitive NHL-B cells. Bax protein levels were analyzed and found to be up-regulated in L-ATRA-sensitive NHL-B cells. Similar results were observed in sensitive AIDS/lymphoma cell lines. Experiments using an RAR-alpha antagonist (RO 41-5253) showed that both the proliferation inhibition and apoptosis induced by L-ATRA could be blocked in NHL-B cells. The findings of the present study indicate that L-ATRA may possess therapeutic potential in blocking cell proliferation, inducing apoptosis, and

eng

IM

MEDLINE

1044-9523

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NLM

1071-82

pubmed-meshheading:9342185-Apoptosis, pubmed-meshheading:9342185-Benzoates, pubmed-meshheading:9342185-Blotting, Western, pubmed-meshheading:9342185-Cell Division, pubmed-meshheading:9342185-Chromans, pubmed-meshheading:9342185-Dosage Forms, pubmed-meshheading:9342185-Down-Regulation, pubmed-meshheading:9342185-Gene Expression Regulation, Neoplastic, pubmed-meshheading:9342185-Humans, pubmed-meshheading:9342185-Liposomes, pubmed-meshheading:9342185-Lymphoma, AIDS-Related, pubmed-meshheading:9342185-Lymphoma, B-Cell, pubmed-meshheading:9342185-Lymphoma, Large B-Cell, Diffuse, pubmed-meshheading:9342185-Microscopy, Electron, pubmed-meshheading:9342185-Proto-Oncogene Proteins, pubmed-meshheading:9342185-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:9342185-Receptors, Retinoic Acid, pubmed-meshheading:9342185-Tretinoin, pubmed-meshheading:9342185-Tumor Cells, Cultured, pubmed-meshheading:9342185-bcl-2-Associated X Protein

Retinoid-mediated inhibition of cell growth with stimulation of apoptosis in aggressive B-cell lymphomas.

Journal Article, Research Support, U.S. Gov't, P.H.S.