Sodium benzylideneascorbate induces apoptosis in HIV‐replicating U1 cells

Abstract

Ul cells, a suhclone of U937 cells chronically infected with human immunodeficiency virus type 1 (HIV-l), produced HIV-l only in the presence of inducers such as 12-0-tetradecanoxylphorbol 13-acetate (TPA) or tumor necrosis factor (TNF)-a. The expression of HIV-antigen on Ul cells induced by TPA or TNF-a was found to be prevented by sodium 5,6+enzylidene+ascorbate(SBA) in a concentration-dependent manner. Treatment of Ul cells with SBA in the presence of inducers resulted in cell death with cell shrinkage, chromatin condensation and DNA fragmentation into nucleosomal oligomers, characteristics of apoptosis. In contrast, SBA had scarcely any apoptotic effect on Ul cells in the absence of inducers. SBA did not also induce apoptosis in parental U937 cells in the presence or absence of inducers. These results suggest that HIV-replicating Ul cells selectively undergo apoptosis on treatment with SBA.

Genetic and Metabolic Control of the Mitochondrial Transmembrane Potential and Reactive Oxygen Intermediate Production in HIV Disease

“…Vitamin C, by itself, can enhance apoptosis of human lymphocytes and myelogenous leukemia cell lines (Amano et al, 1998;Podmore et al, 1998). These findings can explain the controversial impact of vitamin C treatment on survival of HIV-infected cells (Harakeh et al, 1990;Aoki et al, 1994;Rivas et al, 1997). Additionally, metabolites of vitamin C, a 6-carbon sugar, may also contribute to cell death.…”

“…Combined supplementation of vitamin E and C was found to diminish oxidative stress, serum lipid peroxides, and malondialdehyde in HIV-infected patients (Allard et al, 1998b). Because vitamin C can increase death of HIVinfected cells (Aoki et al, 1994;Rivas et al, 1997), vitamin E alone may have had a more beneficial effect.…”

Novel Phorbol Esters Exert Dichotomous Effects on Inhibition of HIV-1 Infection and Activation of Latent HIV-1 Expression

“…There are also reports of selectively induced apoptotic cell death in U1 cells expressing HIV-1 by TPA (Harada et al, 1988;Matsuyama et al, 1989;Aoki et al, 1994). There are also reports of selectively induced apoptotic cell death in U1 cells expressing HIV-1 by TPA (Harada et al, 1988;Matsuyama et al, 1989;Aoki et al, 1994).…”

“…HIV-1 infected cells are highly susceptible to the apoptosis induced by various agents, including tumour promoting and anti-tumour agents such as sodium benzylideneascorbate. There are also reports of selectively induced apoptotic cell death in U1 cells expressing HIV-1 by TPA (Harada et al, 1988;Matsuyama et al, 1989;Aoki et al, 1994). Since drug-induced apoptosis is generally associated with virus induction it is perceived as being rather harmful in the clinical use of such drug.…”