Cell proliferation, inhibition

DL-10 (35) T cell, fibroblast Suppression of B- and T-cell proliferation. Inhibition of LPS-induced monocyte IL-1, IL-8, and TNF production. Induction of IL-lra. Suppression of free radical release and NO-dependent microbicidal activity of macrophages. 

Cell proliferation inhibition. Cytotoxicity was determined as described previously34 by the colorimetric MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (Fluka) microculture assay on compounds freshly dissolved in DMSO... 

Raloxifene has been shown also to exert a more mild but significant effect on normal myometrium in terms of cell proliferation inhibition, as suggested by a PCNA/TC ratio that is lower in raloxifene than in placebo groups (Palomba et al. 2005b). This finding could explain the observation of a reduced incidence in new tumors observed in premenopausal women treated with 180 mg/d raloxifene (Palomba et al. 2002a). To define the relationship, if any, between prolifer-... 

Drugs that can be used to control tumour cell proliferation inhibit a variety of enzymes, including thymidylate synthase and topoisomerase (Chapter 20). The enzyme aromatase converts a ring in a steroid to an aromatic ring. It converts, for example, adrenal steroid hormones into female sex hormones, which bind to oestrogenic receptors in the ovary or breast and increase the risk of ovarian or breast cancer. Aromatase inhibitors are used to treat patients with breast or ovarian cancers that are sensitive to oestrogen. Unfortunately, none of the inhibitors is specific for enzymes in tumour cells and they can therefore have severe side-effects (Chapter 21). 

Cell proliferation inhibition. Lipoprotein fraction of bran, in cell culture at a concentration of 100 pg/mL, was active vs Sawano cells . 

H Tomoda, K Igarashi, JC Cyong, S Omura. Evidence for an essential role of long chain acyl-CoA synthetase in animal cell proliferation. Inhibition of long chain acyl-CoA synthetase by triacsins caused inhibition ofRaji cell proliferation. JBiol Chem 266 4214-4219, 1991. 

Decrease synthesis of secondary bile acids decrease production of IGF-1 direct antiproliferative effects on colorectal epithelium Modulates bile acid composition inhibits cell proliferation Inhibit cellular proliferation and induce apoptosis... 

Figure 1. Angiogenesis and its Inhibition. Growth factors induce blood capillaries (left) to sprout endothelial cells proliferate. Inhibition (anti-angiogenesis) is effected by the pair H-cortisone + heparin.

Arachidonic acid metabolites have received tremendous attention for their role in carcinogenesis. A link among the enzymes, metabolites, and receptors involved in the Cox and Lox pathways has been established to inflammation and a variety of cancers. Aberrant arachidonic acid metabolism has been shown to play a major role in the development and progression of several cancers. Both the Cox and Lox pathways have been linked to cell proliferation, inhibition of apoptosis, and promotion of angiogenesis. In addition, several clinical, in vitro, and in vivo studies have been conducted to demonstrate the chemopreventive activity of several Cox-2 and 5-Lox inhibitors on several models of cancer. - ... 

Choline kinase phosphorylates choline to give a phosphocholine and participates in glycine, serine and threonine metabolism and glycerophospholipid metabolism. Hemicholinium-7 is the prototypical tool compound used to inhibit CHK. Based on inhibitor studies, it has been proposed that CHK is important for the regulation of cell proliferation. Inhibition of choline kinase is also used to target plasmodium and develop novel antimalarials. A series of papers on pyridinium based inhibitors have been published, but no disclosures of more drug-like molecules have been made. 

Inhibits cytokine production by activated T cells Decreases B cell proliferation Inhibits the actions of colony stimulating factors Slows antibody production Which one of the following agents increases phagocytosis by macrophages in patients with chronic granulomatous disease ... 

Inhibition of smooth muscle cell proliferation inhibition of inflammatory processes modulation of gene expression prevention of lipid and lipoprotein (LDL) oxidation - - - - ... 

Superoxide dismutase Inhibition of cell proliferation Inhibition of inflammation Induction of cell-cycle arrest Induction of apoptosis Inhibition of signal transduction pathways Antiangiogenesis... 

LT-lla/LT-llb) Activates splenic DC in vitro" Induces apoptosis of CD8 T-cells and inhibits CD4 T-cell proliferation" Inhibits LPS-induced NF-xB activation and cytokine secretion in monocytes" B subunits interact with TLR2 and can activate monocytes "... 

N-Hydroxyamino acids, similar in action to N-hydroxyurea, some N-hydroxyamides and some aromatic hydroxy acids, are inhibitors of ribonucleotide reductases 112), a unique group of metalloenzymes, essential for cell proliferation. Inhibition of substrate reduction in vitro (l5o = 2.3-10 ) is accompanied by decay of the tyrosyl radical but not the iron atom from the E. coli subunit B2 of this enzyme. Inhibitors of the above type donate an electron to the enzyme s free radical, producing an inactive protein-enzyme with a still intact binuclear iron complex and a new more stable free radical of the nitroxide type (52)... 

Nowadays, an increasing number of biologically active gold NHC complexes have been reported and distinct effects related to tumor cell proliferation inhibition have been confirmed including the increased formation of ROS or apoptosis induction [30,100-102]. 

Figure 45.2 IC50 (50% cell proliferation inhibition concentrations) of the hydrazino-paullone (HP), ligand Lla, and its gallium complex [Ga(Lla-H)2]Cl on different cancer cell lines [54].

The role of NFkB has been reviewed in ref. 205. NFkB is a key regulator of inflammation, immune responses, cell survival, and cell proliferation inhibition of the NFkB pathway in macrophages leads to more severe atherosclerosis in low density lipoprotein receptor (LDLR) deficient mice, possibly by affecting the pro- and anti-inflammatory balance that controls the development of atherosclerosis (reduced production of LPS-stimulated TNF, and reduction in IL-10) (206). 

Cell proliferation inhibition - in vitro (Cell culture, splenoc5hes mouse) vs. cells - CTLL-2 (IC50 0.5 pg/mL), 106... 

After oxidation, the reaction sequence yields the furonaphthoquinones that display submicromolar (IC50) cell proliferation inhibition in human promyelocytic leukemia cells (HL60), thereby outperforming cisplatin (IC50 = 1.9 pM). The effect is expected to derive from the potential to deplete glutathione, either by direct conjugation or via the formation of reactive oxygen species. 

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