Aijin Wang

Modifying Effects of Fungal and Herb Metabolites on Azoxymethane-induced Intestinal Carcinogenesis in Rats

Modifying effects of a fungal product, flavoglaucin, and four plant‐derived chemicals, shikonin, gingerol, oleanolic acid and paeoniflorin, on intestinal carcinogenesis were examined in a rat model using azoxymethane (AOM). A total of 280 male F344 rats, 6 weeks old, were divided into 12 groups. Group 1 (30 rats) was given two subcutaneous injections of 15 mg/kg of AOM at the start of the experiment. Groups 2 (30 rats), 3 (20 rats), 4 (20 rats), 5 (30 rats) and 6 (30 rats) received a test chemical (flavoglaucin, shikonin, gingerol, oleanolic acid or paeoniflorin, respectively) in the diet at a concentration of 0.02% for 3 weeks, during which time AOM was applied, and then kept on basal diet until the end of experiment (one year). Groups 7–11 (each 20 rats) were given a test chemical corresponding to Groups 2–6, respectively. Group 12 (20 rats) served as a control. The incidence and average number of intestinal tumors in Group 2 (47%, 0.57 ± 0.68) were significantly less than in Group 1 (74%, 1.07 ± 0.87) (P < 0.05, respectively). Multiplicity of intestinal neoplasms of Group 3 (0.55 ± 0.60) or 4 (0.47 ± 0.51) was also significantly smaller than that of Group 1 (P < 0.05 and P < 0.01, respectively). These results suggest that flavoglaucin, shikonin and gingerol might be promising chemopreventive agents for intestinal neoplasia.

Different expression patterns of cyclins A, D1 and E in human colorectal cancer.

The expressions of cyclins A, D1 and E at the protein level were investigated by Western blotting in human colorectal carcinomas and in adjacent non-neoplastic colorectal mucosas. Cyclin E was higher in the cancer tissue than in the non-neoplastic mucosa in 92% patients (35 out of 38 cases). However, the cyclin A expression of the mucosa was higher than that of the cancer tissue in 63% (25 out of 40 cases) cases, and only 4 (10%) cancers had higher cyclin A expression. Eleven cancers (27%) demonstrated expression equivalent to that in the mucosa. Equal expression of cyclin D1 in cancer and mucosal tissues was found in 51% cases (20/39), lower expression of cyclin D1 by cancer tissues was demonstrated in 41% cases (16/39) and only three cancers showed higher expression than the mucosa. Proliferating-cell nuclear antigen immunohistochemistry revealed that the labeling index of the cancer tissue was 43.5±8.3% while that of the mucosa was only 14.8±5.1%. These results proved that colorectal cancers express high levels of cyclin E, consistent with a high rate of cell proliferation, whereas most of such cancer lose control of cyclin A and cyclin D1 expression.

Localization of Bax and Bcl-2 proteins, regulators of programmed cell death, in the human central nervous system

Bax and Bcl-2 proteins are identified as regulating molecules for programmed cell death. In the central nervous system, programmed cell death or apoptosis is considered to be an important phenomenon that is related to neuron vulnerability to a variety of toxic effects, including ischaemic insult. In this study, localization of Bax and Bcl-2 proteins was investigated in the human central nervous system using autopsy cases without any neurological disorder. Results were compared with findings in the rat. Most neurons in human cerebral cortex, basal ganglia and brain stem were positive for both Bax and Bcl-2 proteins, whereas Purkinje cells in cerebellum and neurons in hippocampal CA1, CA2 and CA3 regions were positive for Bax but negative or weakly positive for Bcl-2. Glial cells examined in all sections were negative for both proteins. Choroid plexus, ependymal cells and arachnoid villi showed positive reactivity for both proteins. A possible relationship between the localization of Bax or Bcl-2 proteins and the cell vulnerability in central nervous system is discussed.

Inhibitory effects of magnesium hydroxide on c-myc expression and cell proliferation induced by methylazoxymethanol acetate in rat colon

The effects of magnesium hydroxide were examined on methylazoxymethanol (MAM) acetate-induced c-myc expression and cell proliferation of colonic mucosal epithelium in rats. Rats were divided into four groups and treated as follows: MAM acetate alone (25 mg/kg i.p. injection, five times, once a week for 5 weeks), MAM acetate and feeding of 0.2% magnesium hydroxide in diet, magnesium hydroxide alone and non-treatment. At 4, 8 and 16 weeks after the start of experiment, 10 rats in each group were sacrificed. Magnesium hydroxide inhibited the MAM-induced expression of c-myc proto-oncogene, and also suppressed the increased bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) labelling indexes induced by MAM acetate in colon mucosa in initiation and post-initiation phase. These results suggest that the anti-carcinogenic effect of magnesium hydroxide on rat colon carcinogenesis induced by MAM acetate may be related to the inhibition of the carcinogen-induced expression of c-myc proto-oncogene and cell proliferation.

Chemopreventive Effects of Magnesium Hydroxide on Colon Carcinogenesis

The suppression by magnesium hydroxide (Mg(OH)2) of rat colon carcinogenesis was examined in two different experiments. The modification by Mg(OH)2 of cell proliferation in the colon mucosa was also analyzed. Mg(OH)2 reduced the number of colon tumors induced by methy-lazoxymethanol (MAM) acetate or 1,2-dimethylhydrazine. In both experiments, the relationship between the dose of Mg(OH)2 and the tumor-suppressing effect was not strong. Mg(OH)2 suppressed MAM-acetate-induced 5-bromo-2’-deoxyuridine (BrdU) labeling in colon mucosa. The decrease in BrdU labeling indices was more prominent in the proximal segment than in the distal segment. A clear relationship between the dose of Mg(OH)2 and the BrdU labeling index was not found. Mg(OH)2 suppressed the MAM-acetate-induced expression of the c-myc proto-oncogene, and also reduced the increased proliferating cell nuclear antigen (PCNA) labeling induced by carcinogen in colon mucosa, in the same way as with BrdU labeling. The elevation in the BrdU labeling index induced by cholic acid was also suppressed by Mg(OH)2 or by calcium lactate. The inhibitory effect on cell proliferation by Mg(OH)2 may be related to the suppressive action of magnesium on carcinogen-induced colon carcinogenesis. Mg(OH)2 could be a promising chemopreventive agent for human colon neoplasia.