morin and Precancerous-Conditions

Chemopreventive agents are used to diminish the morbidity and mortality of cancer by delaying the course of carcinogenesis. Formation of ACF and amplified activity of colon biotransforming enzymes were considered to be hallmarks of colon carcinogenesis. Morin, a bioflavonoid present in fruits and show various pharmacological and biological activities. Our present study, shows the modulatory effect of morin administration on 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) in rat colon, and fecal and mucosal biotransforming enzyme activities. A total of 64 rats were randomized into four groups. Group 1 served as control, groups 2 and 4 received 50mg/kg b.w. of morin intragastrically for the entire period of the study (30 weeks). Groups 3 and 4 received subcutaneous injection of DMH (20mg/kg b.w.) for 15 weeks. Rats were sacrificed at the end of 30 weeks. The incidence of tumors/polyps in the colon cancer of rats and treated with morin showed reduced incidence (40%) of tumors, as compared to DMH (100%) treated rats. Morin administration significantly reduced ACF formation and lowered the activities of fecal and mucosal biotransforming enzymes. Our findings suggest that morin (50mg/kg b.w.) may be a possible chemopreventive agent against colon cancer.

Topics: 1,2-Dimethylhydrazine; Animals; Antioxidants; beta-Glucosidase; Carcinogens; Colon; Colonic Neoplasms; Disease Models, Animal; Flavonoids; Glucuronidase; Intestinal Mucosa; Male; Nitroreductases; Polysaccharide-Lyases; Precancerous Conditions; Rats; Rats, Wistar

The modifying effect of dietary exposure to a flavonoid morin during the initiation and post-initiation phases of azoxymethane (AOM)-initiated colorectal carcinogenesis was investigated in male F344 rats. A total of 55 animals were initiated with AOM by weekly s. c. injections of 15 mg/kg body wt for 3 weeks to induce colorectal neoplasms. Rats were fed a diet containing 500 p.p.m. morin for 5 ('initiation feeding') or 28 ('post-initiation feeding') weeks. Other groups contained rats treated with morin alone (500 p.p.m. in diet) and untreated rats. At the end of the study (32 weeks), the incidence of adenocarcinoma in the large intestine of rats initiated with AOM together with (43%) or followed by (29%) a diet containing morin was smaller than that of rats given AOM alone (75%). A significant difference was found between 'post-initiation feeding' and untreated groups (P = 0.023). Although both 'initiation feeding' and 'post-initiation feeding' of morin reduced polyamine levels in colorectal mucosa and blood, 'post-initiation feeding' of morin significantly decreased the proliferating cell nuclear antigen-positive index in aberrant crypt foci. 'Post-initiation feeding' of morin significantly elevated glutathione S-transferase and quinone reductase activities in the liver and large bowel, but 'initiation feeding' caused a significant elevation of these enzymes activities only in the large bowel. These results indicate that morin could exert a weak chemopreventive effect on large bowel tumorigenesis induced by AOM when fed during the post-initiation phase.

Topics: Adenocarcinoma; Adenoma; Animals; Anticarcinogenic Agents; Antioxidants; Azoxymethane; Carcinogens; Colorectal Neoplasms; Drug Screening Assays, Antitumor; Flavonoids; Glutathione Transferase; Male; Polyamines; Precancerous Conditions; Rats; Rats, Inbred F344

The modifying effects of dietary exposure of the flavonoid morin on 4-nitroquinoline 1-oxide (4-NQO)-induced tongue tumorigenesis, the activities of phase II detoxifying enzymes glutathione S-transferase (GST) and quinone reductase (QR) in liver and tongue, and cell proliferation activity in tongue were investigated in male F344 rats. At 7 weeks of age, all animals except those treated with morin alone and control group were given 4-NQO (20 ppm) in drinking water for 8 weeks to induce oral neoplasms. Starting 7 days before 4-NQO exposure, experimental groups were fed experimental diets containing morin (100 and 500 ppm) for 10 weeks ("initiation feeding"). Starting 1 week after the cessation of exposure to 4-NQO, other experimental groups given 4-NQO and a basal diet were given experimental diets for 22 weeks ("post-initiation feeding"). At week 32 week, "initiation feeding" of morin caused a significant reduction in the incidence of tongue carcinoma (by 44-100%). "Post-initiation feeding" with morin also significantly decreased the frequency of tongue carcinoma (by 44%). Morin feeding elevated liver GST and QR activities and GST activity in the anterior portion of tongue. Feeding with morin significantly lowered QR activity of the posterior part of the tongue. Dietary exposure to morin significantly decreased the proliferating cell nuclear antigen-positive index in the posterior portion. Also, morin feeding lowered tongue polyamine levels, especially in the "post-initiation feeding" group. Our results indicate that morin acts as a chemopreventive agent against tongue carcinogenesis induced by 4-NQO through modification of detoxifying enzyme activities and/or cell proliferation activities.

Topics: 4-Nitroquinoline-1-oxide; Animals; Anticarcinogenic Agents; Biogenic Polyamines; Diet; Flavonoids; Glutathione Transferase; Male; NAD(P)H Dehydrogenase (Quinone); Precancerous Conditions; Proliferating Cell Nuclear Antigen; Rats; Rats, Inbred F344; Tongue Neoplasms