Respiration inhibition, tumor cells

Bissonnette, E.Y., 1996. Histamine inhibits tumor necrosis factor a release by mast cells through H2 and H3 receptors. Am. J. Respir. Cell. Mol. Biol. 14, 620-626. 

Complete elucidation of the mechanisms by which ricin kills target cells remains an area of active study, but it is clear that the A -glycosidase activity of RTA is the essential triggering event. Inhibition of protein synthesis precedes other detectable alterations in target cell biochemistry. Ricin blocks amino acid incorporation in cmde microsome preparations before changes occur in energy metabohsm or oxidative phosphorylation the toxin has essentially no effect on mitochondrial respiration in isolated mitochondria or tumor cells (Waller et al., 1966 Dirheimer et al., 1968 Lin et al., 1971). Likewise, the first observable cytotoxic effect of ricin in cell culture is typically the inhibition of protein synthesis, followed by a reduction in DNA synthesis (Lin et al., 1970 Lin et al., 1971 Onozaki et al., 1972 Refsnes et al., 1974 Nicolson et al., 1975 Olsnes et al., 1976 Refsnes et al., 1977). 

Pavani M, Fones E, Oksenberg D, Garcia M, Hernandez C, Cordano G, et al. Inhibition of tumoral cell respiration and growth by nordihydroguaiaretic acid. Biochem Pharmacol 1994 48 1935 12. 

NDGA has been shown to have antitumor activity in vivo and in vitro. It is a powerful cancer antimetabolite producing in vitro complete inhibition of aerobic and anaerobic glycolysis and respiration of suspensions of several types of tumor cells including leukemia types. In vivo, NDGA combined with ascorbic acid is reported to reduce... 

It is now well established that NO also has a number of cGMP-indepen-dent actions. The cytotoxic effects of NO (e.g., on tumor cells) involve the inhibition of tumor cell NADHmbiquinone oxidoreductase, NADH succi-nate oxidoreductase, cis-aconitase, and all iron-sulfur prosthetic groups of the enzymes that contain them. When tumor cells are cocultured with activated macrophages, they release iron, and the amounts of iron released correlate with a decrease in cellular respiration and replication (Stuehr and Nathan, 1989 Nathan, 1992). 

The different nature of MR, as compared to hydrophobic and steric properties, can only be detected in cases where a proper selection of substituents allows this. One sueh example is the inhibition of malate dehydrogenase by 4-hydroxyquinoline-3-carboxylic acids (5), where the interaction of the ligands with the enzyme is described better by MR (eq. 36) than by Jt (pljo vs. Ji n = 13 r = 0.604 s = 0.716), and the respiration inhibition of ascites tumor cells, where the transport into or the accumulation in the cells is more appropriately described by Jt (eq. 37 same set of compounds) than by MR (piso vs. MR n = 14 r = 0.699 s = 0.554) (Table 9) [293]. 

Berberine inhibits oxidative decarboxylation of yeast pyruvic acid (310) the same dose has, however, no effect upon aerobic glycolysis, Warburg s respiratory enzymes, indophenol oxidase, etc. Berberine and tetrahydroberberine have an inhibitory effect on oxidation of (+ )-alanine in rat kidney homogenates (498). Berberine and palmatine show a specific inhibitory effect upon cholinesterase in rabbit spleen and on pseudocholinesterase in horse serum (499). Berberine inhibits cellular respiration in ascitic tumors and even in tissue cultures (500-502). The specific toxic effect of berberine on the respiration of cells of ascitic tumors in mice was described (310). The glycolysis was not found to be affected, but the uptake of oxygen was smaller. Fluorescence was used in order to demonstrate berberine in cellular granules. Hirsch (503) assumed that respiration is inhibited by the effect of berberine on the yellow respiratory enzymes. Since the tumorous tissue contains a smaller number of yellow respiratory enzymes than normal tissue it is more readily affected by berberine. Subcutaneous injections of berberine, palmatine, or tetrahydropalmatine significantly reduce the content of ascorbic acid in the suprarenals, which is not affected by hypophysectomy (504). 

Watson, M.L., Smith, D., Bourne, A.D., Thompson, R-C. and Westwick, J. (1993). Cytokines contribute to airway dysfunction in antigen-challenged guinea pigs inhibition of airway hyperreactivity, pulmonary eosinophil accumulation and tumor necrosis fitctor generation by pretreatment with an interleukin-l receptor antagonist. Am. J. Respir. Cell. Mol. Biol. 8, 365-369. 

Geng, Y., Hansson, G. K., and Holme, E. (1992). Interferon-y and tumor necrosis factor synergize to induce nitric oxide production and inhibit mitochondrial respiration in vascular smooth muscle cells. Circ. Res. 71, 1268-1276. 

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