Apoptosis promoters

Two possibly related phenomena have been found to be dependent on the flux of monovalent ions. The hypothetical common link is represented by a newly discovered family of intracellular proteases whose activity may be influenced by concentrations. Interleukin converting enzyme (ICE) is the best studied member of this family. Efflux of from monocytes leads to activation of ICE, so that the cells rapidly process and export IL-16 (Walev etal., 1995). An ICE-related protease is involved in regulating programmed cell death, which may be the reason why formation of K -permissive pores by alpha-toxin in human T-lymphoctes causes apoptosis (Jonas et a/., 1994). Both apoptosis and ICE-activation are inhibited when alpha-toxin treated cells are suspended in K" -rich medium. It is of interest that simultaneous flooding of cells with Ca , such as occurs when larger pores are formed in lymphocytes (e.g. at high alpha-toxin concentrations or with . coli hemolysin) counteracts the apoptosis-promoting effect of K -efflux (Jonas et a/., 1994). 

Stayrock, K.R., J.H. McKinzie, Y.D. Burke, Y.A. Burke, and P.L. Crowell, 1997. Induction of the apoptosis-promoting protein Bak by periUyl alcohol in pancreatic ductal adenocarcinoma relative to untransformed ductal epithelial cells. Carcinogenesis, 18 1655-1658. 

The predominant effect of flavonoid and isoflavonoid supplementation in ex vivo cell culture models appears to be one of promoting apoptosis [54—57]. This is repeatedly observed in studies witti transformed cancer cells, leading to the descriptions cytoprotective and/or chemopreventive [6,58]. Two poly-phenolic compounds that have been extensively studied in anticancer research are quercetin and genistein, a flavonoid and isoflavone, respectively. However, ex vivo studies with primary cultured cells in 2000 and 2001 showed that some flavonoids can prevent apoptosis promoted by agents that induce oxidative stress [7,8,59]. The outcome of flavonoid treatment is expected to show a complex dependence on a number of factors, including the type of flavonoid, its concentration, the type of cell (e.g., transformed versus nontransformed), the mechanisms of action of the flavonoid, the nature of the proapoptotic stimulus, and the specific apoptotic signaling pathway that is activated. 

Protein kinase A activation usually promotes, whereas protein kinase C activation retards, apoptosi.s. 

S. Increased synthesis of transforming growth factor-beta , which blocks cell division and promote.s apoptosis by interacting with its own membrane recepror,... 

Integrin otvfi3 Antagonists Promote Tumor Regression by Inducing Apoptosis of Angiogenic Blood Vessels... 

Decitabine (5-aza-deoxycytosine) is an analog of the nucleoside 2 -deoxycytidine. It is believed to exert its antineoplastic effects after phosphorylation and direct incorporation into DNA and by inhibition of the enzyme DNA methyltransferase, causing hypomethylation of DNA and cellular differentiation or apoptosis. DNA hypomethylation is achieved at concentrations below those required to significantly inhibit DNA synthesis, which may promote restoration of function to genes associated with control of cellular differentiation and proliferation. Cytotoxicity in rapidly dividing cells may also result from covalent adducts between DNA methyltransferase and decitabine. 

BID is a member oftheBcl-2 gene family, which encode proteins that function either to promote apoptosis or to inhibit apoptosis as in the proteins derived from Bcl-2. These proteins can exist as monomers or they can dimerize. For example, if two promoting Bcl-2 family proteins dimerize then apoptosis will be greatly enhanced. Conversely, if dimerization of an inhibitory and promotor protein occurs, then the effects are cancelled out. The Bcl-2 family of proteins are localized to the outer mitochondrial or outer nuclear membranes. 

Transforming growth factor-beta (TGF- 3) proteins are multifunctional morphogens that control cell proliferation, differentiation and apoptosis, as well as cell migration and immune surveillance. TGF-(3 acts as a tumor suppressor, but can also act as a tumor promoter in... 

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