ODC, activity

In addition to okadaic acid, dinophysistoxin-1 (i.e., 35-methylokadaic acid), 7-0-palmitoyl-okadaic acid, and pectenotoxin 2 are reported to be diarrhetic toxins from shellfish 34). Application of 1 xg of dinophysistoxin-1 to mouse ear caused as strong irritation as the same dose of okadaic acid. Interestingly, the potencies of these compounds in the irritant test on mouse ear correlated well with their potencies as diarrhetic shellfish poisons. Dinophysistoxin-1 induced ODC activity as strongly as okadaic acid. Recently, we found that dinophysistoxin-1 is also a new non-TPA type tumor promoter with as high activity as okadaic acid 35). 

Induction of epidermal ODC is a characteristic biochemical alteration elicited by TPA and may be representative of the effects of phorbol esters with strong tumor promoting activity [81]. A single application of TPA (5 pg) resulted in a substantial and transient increase of epidermal ODC activity in mice with a peak at about 4 h after TPA treatment, and the induction was potently inhibited by treatment (5 pM) of the mouse skin with sitosterol (33, 65% inhibition) and three lupane type triterpenoids betulin (255 79%), betulinic acid (257 89%), and lupeol (264,96%) [30]. The inhibitory effect on TPA-induced ODC activity was further reported for ursolic acid (210 45% inhibition at 2.0 pM/5nM of TPA) [31]. 

The mechanisms by which antitumor-promoters suppress the tumor promotion are not known, but may be due to the following effects (i) inhibition of polyamine metabolism (ii) inhibition of arachidonic acid metabolism (iii) protease inhibition (iv) induction of differentiation (v) inhibition of oncogene expression (vi) inhibition of PKC and (vii) inhibition of oxidative DNA damage [3,6,91]. The polyamine content of cells is correlated to their proliferative, and often, their neoplastic capabilities. A key enzyme in the polyamine biosynthetic pathway, ornithine decarboxylase (ODC), catalyzes the convertion of ornithine to putrescine. Phorbol ester promoters such as TPA cause increased ODC activity and accumulation of polyamines in affected tissues. Diacylglycerol activated PKC, and the potent tumor promoter, TPA, binds to, and activates PKC, in competition with diacylglycerol. PKC stimulation results in phosphorylation of regulatory proteins that affect cell proliferation. Some chemopreventive agents have inhibitory activity towards PKC. Refer to recent review articles for further discussion [3,6,91]. 

Table III. Comparison of Serum-induced ODC Activity with CMP-NeuAc lactosylceramide Sialyltransferase Activity in Various Cell Lines...

Non-bracketed numbers ODC activity nmoles/mg protein/hr Bracketed numbers Sialyltransferase Activity pmoles/mg protein/hr... 

Figure 6. Effect of fresh serum-containing media on ODC activity in logarith-mically growing KB cells. A11 = 0 fresh media added to one set of cultures with no addition to the other set. ODC activity then measured every 2 hr after media...

Figure 7. Effects of various sera on ODC activity in KB cells. To log-phase KB cells, fresh media containing (a) no serum, (b) 10% calf serum, (c) 10% heat-inactivated calf serum, or (d) 10% dialyzed calf serum was added ft= 0). ODC activity then measured every 2 hr under each condition listed.

Ornithine decarboxylase catalyzes the transformation of ornithine to the polycationic bases, putresine, spermine, and spermidine. These compounds exert regulatory effects on cell growth. It has been shown that quercetin (10 to 30 pmol/mouse) markedly suppressed the stimulatory effect of the transporters associated with antigen processing (TPA) on ornithine decarboxylase (ODC) activity and on skin tumor formation in mice initiated with dimethylbenzanthracene. Such inhibition may be related to the activation of the catalytic site, which is under nonconventional regulation by small molecules. Also, the synthetic flavonoid flavone acetic acid was shown to inhibit the activity of ODC in stimulated human peripheral blood lymphocytes and human colonic lamina propria lymphocytes. 

Ornithine decarboxylase (ODC) is the first enzyme in the polyamine biosynthesis pathway. Polyamines play essential roles in cell proliferation and differentiation and participate in macromolecular synthesis. Inhibitors of ODC block aspects of tumor promotion and induce cellular differentiation in several animal carcinogenesis models. Thus induction of ODC has been implicated as being important to carcinogenesis, and ODC activity is an intermediate biomarker of cell proliferation in studies... 

We first assessed the effects of apigenin on ornithine decarboxylase (ODC) activity, a marker of cell proliferation, in cultured human colon cancer cells (Caco-2). ODC activity was measured by assessing the release of CO2 from 1-C -ornithine. Apigenin treatment for 15 to 39 h at 10 or 30 pM inhibited the ODC in the cultured colonic Caco-2 cells by 26 5 and 57 12%, respectively, when compared with the vehicle (p < 0.01). Studies in CF-1 mice determined dietary apigenin effects on ODC and ACF, precursors of colon cancer. These studies in mice demonstrated that dietary apigenin fed at 0.1 % for 1 week reduced the colonic basal ODC activity by 42 23% in comparison with control diet (p < 0.01). Because ODC was inhibited by only 1 week of dietary apigenin at... 

Recent developments in cellular biology have demonstrated the important role of mitogenic signal transduction in controlling the tumor proliferation. The induction of ornithine decarboxylase (ODC), PKC, protein kinase activities, and oxidative stress by the phorbol ester, TPA, is believed to be closely related to the tumor promotion activity of this compound. Topical application of green tea polyphenols to mouse skin was found to inhibit TPA-caused induction of ODC activity in a dose-dependent manner. Our studies demonstrated that EGCG and TF-3 inhibited TPA-induced transformation, PKC activation, and AP-1 binding activities in mouse fibroblast cells. ... 

Figure 3. Effect of pentachlorophenol on the N-hydroxy-2-acetyl-amlnofluorene-induced increase in ornithine decarboxylase (ODC) activity in rat liver. N-hydroxy-2AAF or 2AAF was administered i.p. <94 and 63 Jmol/kg i.p. respectively). One hour prior to N-hydroxy-2AAF, pentachlorophenol <40 ymol/kg) was given. ODC was measured in liver cytosol. (Reproduced with permission from Ref. 23. Copyright 1984, Marcel Dekker.)...

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