Programmed Cell Death Studies

To further assess the relationship of ascorbic acid to tumor cell growth control, studies were conducted to observe the development of programmed cell death. If ascorbic acid was inhibiting tumor cell growth, as exemplified by the development of programmed cell death, was the agent functioning as a prooxidant or antioxidant  

An immunoblot indicated that the level of the protein Bcl-2 was depressed when ascorbic acid was applied to tumor cells at a concentration of 70 p,M. Additional studies indicated that ascorbic acid at concentrations as low as 20 xM-1.25 p,M produced nucleosome formation (DNA fragmentation) of some of the tumor cells in a dose-dependent manner (Figs. 8 and 9). Subsequently, a determination of reduced levels of total mercaptans and intracellular levels of glutathione further suggested a prooxidant characteristic to the ascorbic acid treatment of the oral carcinoma cells (Figs. 10 and 11). 

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The morphological and biochemical characteristics of apoptosis are not always manifest in cells undergoing programmed cell death. Studies have clearly... 

Programmed cell death plays an important role during lymphocyte development, by eliminating autoreactive cells, as well as in the effector phase of the immune response, when antigen induced cell death halt cell activation. Several groups have been studied the function of PTEN in the immune response. PTEN heterozygous (PTEN+/-) mutants develop a lethal polyclonal autoimmune disorder with features reminiscent of those observed in Fas-deficient mutants. Fas-mediated apoptosis was impaired in Pten+/-mice, and T lymphocytes from these mice show reduced activation-induced cell death and increased proliferation upon activation. PI3-K inhibitors restored Fas responsiveness in PTEN+/- cells. These results indicate that PTEN is an essential mediator of the Fas response and a repressor of autoimmunity, thus implicate the P13-Kinase/Akt pathway in Fas-mediated apoptosis (DiCristofano et al, 1999)... 

Sheep anti-FITC-POD (Roche). Primary antibodies in this study we have used a mouse monoclonal antibody against smooth muscle a-actin (sm-a-actin, Dako) and rabbit polyclonal antibody against programmed cell death 4 (PDCD4, Rockland Immunochemicals). 

Neuronal cell death is required for the development of the nervous system. However, recent studies suggest that neurons die from programmed cell death (apoptosis) in brains deprived of oxygen by stroke [14] and trauma [15], and in the brains of Alzheimer s patients [16], Therefore, prevention of neuronal apoptosis has been considered to be a desirable therapeutic strategy for treating such neurodegenerative diseases, although the value of this approach is not yet evident. We have recently reported that crocin suppresses tumor necrosis factor (TNF)-a-... 

Volume 442. Programmed Cell Death, General Principles for Studying Cell Death (Part A)... 

The benzyl-substituted titanocene 3, which showed a significant higher cytotoxicity when tested in vitro against LLC-PK, was evaluated in a series of biomedical studies as well. Watson et al. tested titanocene 3 in comparison to two aryl-substituted tf .va-titanocenes on prostate cancer cells, as advanced prostate cancer is not curable up to now [37]. Therefore, it was shown that all three titanocenes induced more apoptosis (programmed cell death, in contrast to necrosis) compared with cisplatin in a dose-dependent manner. Titanocene 3 had the most significant effect on the cell cycle and apoptosis. 

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