Cell inhibition

Taxanes (paclitaxel, docetaxel) are derivatives of yew tree bark (Taxus brevifolia). They stabilize microtubules in the polymerized state leading to nonfunctional microtubular bundles in the cell. Inhibition occurs during G2- and M-phases. Taxanes are also radiosensitizers. Unwanted effects include bone marrow suppression and cumulative neurotoxicity. 

Lymphocytes, inflammatory cells, intestinal mucosal cells, cartilage cells and bone precursor cells Inhibition of proliferation... 

Other tissues/cells Inhibition of growth factor (IGF 1, EGF, PDGF)and cytokine (IL6, IFN-y) secretion... 

RevMlO CD34+ bone marrow cells Inhibits HIV-1 Rev-mediated transactivation of HIV-1 gene expression Podsakoff et al. 2005... 

Dunlop DJ, Wright EG, Lorimore S, et al. Demonstration of stem cell inhibition and myeloprotective effects of SCI/rhMIPl alpha in vivo. Blood 1992 79(9) 2221-2225. 

Tanshinones isolated from the dried root of Salvia miltiorrhiza Bunge abrogated the survival of P388 lymphocytic leukemia cells cultured in vitro. Tanshinone I and tanshinone IIA showed 86.76 and 56.05% cell inhibition, respectively, at a dose of 25 pig/mL) (54). Dihydrotanshinone I and cryptotanshinone were relatively cytotoxic (55). Dihydrotan-shinone I induces cell growth anest during the S phase and, subsequently, apoptosis. 

Ajoene has antitumor activity, inhibits cholesterol biosynthesis, modulates membrane-dependent functions of immune cells, inhibits protein prenylation83 and is an anti-leukaemia agent for acute myeloid leukaemia.85 In antithrombotic assays, the Z isomer is more active than the E isomer.84... 

Inhalation route adults subjected to 50,000 or 200,000 pg acrolein/L (113 or 454 mg/m3) air via an endotracheal cannula for up to 27 days Air sac injection route embryos 2-3 days old examined at day 13 Decreases in trachea complement of ciliated and goblet cells inhibited mucus transport activity in trachea lymphocytic inflammatory lesions in the tracheal mucosa changes were more pronounced at the higher dose and with increasing exposures 2... 

Benjamin, N., Dutton, J. A. E., Ritter, J. M., Human vascular smooth muscle cells inhibit platelet aggregation when incubated with glyceryl trinitrate evidence for generation of nitric oxide. Br. J. Pharmacol. 102 (1991), p. 847-850... 

The inhibition of amino-acid transport has been regarded as the main toxic effect of mercury compounds [82], The biochemical mechanism underlying the inhibition is unclear. In unfertilized sea-urchin eggs an interaction with the amino-acid carrier was found, whereas in fertilized eggs inhibition of amino-acid transport was indirect and might result from an elevation of the Na + content of the egg caused by the inhibition of the Na+ pump [83]. The action on the diffusional process could be mediated by an effect on membrane phospholipids or on membrane proteins, or by interaction with Ca2+ which stabilizes membrane structure. Mercuric chloride in skate liver cells inhibited amino acid transport, decreased Na + /K + -ATPase (adenosinetriphosphatase) activity, impaired volume regulatory mechanisms and increased the permeability of the plasma membrane to potassium [84]. It has been suggested that... 

Catectin promotes tumor cytotoxicity activates macrophages and neutrophils enhances IL-2 receptor expression on T cells inhibits antibody secretion... 

Cyclosporin A Transplant rejections Depresses T cells inhibits IL-2 production... 

Disulfoton and its breakdown products can be measured in the blood, urine, feces, liver, kidney, or body fat of exposed people. In cases of occupational or accidental exposure to disulfoton, the breakdown products are often measured in the urine. The breakdown products are relatively specific for disulfoton and a few other similar organophosphate pesticides and can be detected in urine for up to one week after people were last exposed. Because disulfoton inhibits cholinesterase in blood and in blood cells, inhibition of this enzyme activity may also suggest exposure to disulfoton. Cholinesterase activity in blood and in blood cells may remain inhibited for as long as 1-2 weeks after the last exposure. Because other organophosphate pesticides also inhibit cholinesterase activity in blood and blood cells, this test is not specific for disulfoton. The measurement of cholinesterase in blood and blood cells and the amount of disulfoton breakdown products in the urine cannot always predict how much disulfoton you were exposed to. Your doctor can send samples of your blood or urine to special laboratories that perform these tests. Chapters 2 and 6 provide more information about medical tests. 

Cell inhibition rate analysis Cells were seeded in 96-well plates at a density of 1.5/ 104 cells/well in quadruplicate and incubated at 37°C in a 5% C02 atmosphere. After 24 hr, cells were treated with 0.1% DMSO (control) or, compound at various concentrations (0.01 - 0.33 mM) for 48 hr. Cell inhibition rate was analyzed after 48 hr using the Cell Counting Kit CCK-8 (Dojindo Laboratories, Japan), according to the manufacturer s instructions. OD values were measured at a wavelength of 450 nm using a Multi-Detection Microplate-Reader (Bio-TEK, Winooski, VT). 

Perloff MD, von Moltke LL, Greenblatt DJ (2002) Fexofenadine transport in Caco-2 cells Inhibition with verapamil and ritonavir. J Clin Pharmacol 42 1269-1274. 

W. J. Chang, K. G. Rothberg, B. A. Kamen, and R. G. Anderson. Lowering the cholesterol content of MA104 cells inhibits receptor-mediated transport of folate. J. Cell Biol. 118 63-69 (1992). 

Binds to DNA and prevents separation of the helical strands Affects neuronal transmissions Binds to opiate receptors and blocks pain pathway Acts as central nervous system depressant Inhibits Na/K/ATPase, increases intracellular calcium, and increases ventricular contractibility Blocks the actions of histamine on Hi receptor Blocks ai-adrenergic receptor, resulting in decreased blood pressure Inhibits reuptake of 5-hydroxytryptamine (serotonin) into central nervous system neurons Inhibits cyclooxygenase, inhibition of inflammatory mediators Inhibits replication of viruses or tumor cells Inhibits HIV reverse transcriptase and DNA polymerase Antagonizes histamine effects... 

Recently, it has been shown that cell-permeable cerantides dramatically inhibited the synthesis of the two major membrane phospholipids, PC and PE (Bladergroen et al, 1999b Allan, 2000). The inhibition of phospholipid synthesis was rapid, within 2 h, and resulted in massive apoptosis after 16-24 h. The mechanism by which short-chain cerantides exert their effect on phospholipid synthesis is possibly cell type dependent. In baby-hamster kidney (BHK) fibroblasts rc synthesis was reduced at the level of CT, the putative rate-determining enzyme in the CDP-choline pathway (Allan, 2000). This conclusion was based solely on radio-label studies in combination with an earlier published observation (Wieder et al, 1995) showing that C2-SM (the SM generated from C2-ceramide by SM synthase, which was actively synthesized in the BHK-cells) inhibited CT activity in vitro. On the other hand, data obtained from studies with rat-2 fibroblasts clearly showed that short-chain cerantides regulate the synthesis of PC and PE mainly at the final step of the CDP-pathways. This conclusion was based on the following observations (a) incorporation of [ H]-choline into PC and... 

Lewkowicz P. Lewkowicz N, Sasiak A, Tchorzewski H Lipopolysaccharide-activated CD4-I-CD25+ T regulatory cells inhibit neutrophil function and promote their apoptosis and death. 

Fields ML, Hondowicz BD, Metzgar MH, Nish SA, Wharton GN, Picca CC, Caton AJ, Erikson J CD4+CD25 + regulatory T cells inhibit the maturation but not the initiation of an autoantibody response. J Immunol 2005 175 4255-4264. 

Adorini L, Penna G, Giarratana N, Uskokovic M Tolerogenic dendritic cells induced by vitamin D receptor ligands enhance regulatory T cells inhibiting allograft rejection and autoimmune diseases. J Cell Biochem 2003 88 227-233. 

Semnani RT, Liu AY, Sabzevari H, et al Brugia malayi microfilariae induce cell death in human dendritic cells, inhibit their ability to make IL-12 and IL-10, and reduce their capacity to activate CD44- T cells. J Immunol 2003 171 1950-1960. 

Figure 2 Effect of liposomal formulations BPs (alendronate and clodronate), empty and free drugs on RAW 264 cell survival. Curves represent percentage of cell inhibition with different BP concentrations. Cell count in buffer only was determined to be 100% (n = 3). Abbreviation BPs, bisphosphonates. Source From Ref 69.

Foamed polymers. Thermosets and thermoplastics formed into low density, cellular materials containing bubbles of gas. Rigid foams have their gas bubbles in closed cells, inhibiting flexibility flexible foams have the bubbles in open cells, permitting the gas to escape as the foam is flexed. 

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