Anti-proliferative

Table 4.2 Summary of smdies comparing the anti-proliferative effects against tumour cell lines of glucosinolate metabolites in vitro. The comparisons do not distinguish between increased cell death and reduced rate of cell division...

Coal tar is keratolytic and may have anti-proliferative and anti-inflammatory effects.2 Coal tar products include crude coal tar and tar distillates (liquor carbonis detergens) available as ointments, creams, and shampoos in various strengths. Preparations containing coal tar may precipitate folliculitis,10 will stain clothing, and have an unpleasant odor. They are also photosensitizing and can be combined with UVB phototherapy (Goekermann s regimen) to increase treatment response.19,20... 

D10. Delomenie, C., Wautier-Pepin, M. P, Chappey, O., and Wautier, J. L., Modulation of human endothelial cell activation by anti-proliferative cytokines Exploration of arachidonic acid and intracellular cytokine pathways as possible mechanisms of action. Exp. Cell Res. 257, 122-130 (1993). 

Chor SY, Hui AY, To KF, et al. Anti-proliferative and pro-apoptotic effects of herbal medicine on hepatic stellate cell. J Ethnopharmacol 2005 100 180-186. 

Pihie AHL, Stanslas J, Din LB. Non-steroid receptor-mediated anti-proliferative activity of styrylpyrone derivative in human breast cancer cell lines. Anticancer Res 1998 18 1739-1743. 

Roy MK, Takenaka M, Isobe S and Tsushida T. 2007. Antioxidant potential, anti-proliferative activities, and phenolic content in water-soluble fractions of some commonly consumed vegetables effects of thermal treatment. Food Chem 103(1) 106-114. 

Most cytokines are pleiotropic, i.e. can affect a variety of cell types. Moreover, the effect that a cytokine has on one cell type may be the same or different to its effect on a different cell type. IL-1, for example, can induce fever, hypotension and an acute phase response. G-CSF is a growth factor for neutrophils, but it is also involved in stimulating migration of endothelial cells and growth of haematopoietic cells. IFN-y stimulates activation and growth of T- and B-lymphocytes, macrophages, NK cells, fibroblasts and endothelial cells. It also displays weak anti-proliferative activity with some cell types. 

Interferons induce a wide range of biological effects. Generally, type I interferons induce similar effects, which are distinct from the effects induced by IFN-y. The most pronounced effect of type I interferons relates to their antiviral activity, as well as their anti-proliferative effect on various cell types, including certain tumour cell types. Anti-tumour effects are likely due not only to a direct anti-proliferative effect on the tumour cells themselves, but also due to the ability of type I interferons to increase NK and T-cytotoxic cell activity. These cells can recognize and destroy cancer cells. 

IFN-y exhibits, at best, weak antiviral and anti-proliferative activity. When co-administered with type I interferons, however, it potentates these IFN-a/p activities. IFN-y is directly involved in regulating most aspects of the immune and inflammatory responses. It promotes activation, growth and differentiation of a wide variety of cell types involved in these physiological processes (Table 8.7). 

The ability of interferons (especially type I interferons) to induce an antiviral state is unlikely to be solely dependent upon the enzymatic mechanisms discussed above. Furthermore the 2 -5 A synthetase and eIF-2a kinase systems may play important roles in mediating additional interferon actions. The ability of such systems to stall protein synthesis in cells may play a role in interferon-induced alterations of cellular differentiation or cell cycle progression. They may also be involved in mediating interferon-induced anti-proliferative effects on various transformed cells. 

The antiviral and anti-proliferative activity of interferons, as well as their ability to modulate the immune and inflammatory response renders obvious their potential medical applicatioa This has culminated in the approval for clinical use of several interferon preparations (Table 8.8). Ongoing clinical trials are likely to expand the medical uses of these regulatory molecules further over the next few years. 

Palomba S, Orio F Jr, Russo T, Falbo A, Tolino A, Lombardi G, Cimini V, Zullo F (2005b) Anti-proliferative and pro-apoptotic effects of raloxifene on uterine leiomyomas in postmenopausal women. Fertil Steril (in press)... 

Isoxazolines are partially unsaturated isoxazoles. In most cases these compounds are precursors to the isoxazoles, and as a result, the synthesis can also be found in Sect. 3.2.1b. Kaffy et al., used a 1,3-dipolar cycloaddition of a nitrile oxide (186) with the respective styrene (201a or b) to generate isoxazolines (202a or b, respectively). Depending on the substitution of the vinyl portion of the styrene molecule, either 3- or 4-substituted isoxazolines could be formed (Scheme 55) [94], Simoni et al. employed similar chemistry to produce isoxazolines [60]. Kidwai and Misra emplyed microwave technology to treat chalcones with hydroxylamine and basic alumina [99]. The isoxazoles synthesized by Simoni et al. possess anti-proliferative and apoptotic activity in the micromolar range [60]. 

Many intracellular targets of sphingosine that may contribute to its apoptotic and anti-proliferative effects have been identified (Figure 2). These include proteins of the bcl-2 family, the retinoblastoma gene product, several enzymes and its ability to interact with DNA (reviewed by Alessenko, 2000). For example, sphingosine-induced apoptosis of HL60 cells correlated with reduced expression of the cell survival protein bcl-2... 

The mechanistic basis of the anti-neoplastic activity of UDCA and the explanation for the significant difference in bioactivity of UDCA compared with DCA despite marked similarity in chemical structure remain unresolved. UDCA administration in healthy volunteers and colorectal adenoma patients has been demonstrated to decrease the proportion of DCA in aqueous phase stool. Therefore, one possible mechanism of the chemopreventative activity of UDCA is reduction of mucosal secondary bile acid exposure. Consistent with this idea, UDCA administration has been demonstrated to reduce the incidence of K-ras mutations and decrease Cox-2 expression in AOM-induced tumors, which is the opposite of the reported effects of DCA in the same model. However, it is clear that exogenous administration of UDCA has direct anti-neoplastic activity on human CRC cells in vitro, either alone or in combination with DCA, including anti-proliferative and anti-apoptotic effects, as well as induction of cell senescence. " ... 

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