naphthoquinones and azomethane

Lawsone (LS) a colored napthoquinone compound obtained from the plant Lawsonia inermis L. (Lythraceae) is known for its usefulness of being a precursor for synthesis of some anticancer compounds. Literatures support potent anticancer activity of napthoquinone derivatives in human colon cancer, present study evaluates the effect and mechanism of LS on chemical induced colon cancerous rats and human colon cancer DLD-1 cells, the study was supported by endoscopy, histological and immunohistochemistry analysis. KAD rats were subjected to colon cancer mediated by Azoxymethane (AOM) injections followed Dextran sodium sulfate (DSS) orally in drinking water. After endoscopic confirmation the rats were given LS (200mg/ml) orally for 8 weeks. Presence of aberrant foci, types of tumors and the proliferative effect on tumor lesions was studied by macroscopic, histological and immunohistochemical analysis. To establish the mechanism, human colon DLD-1 cancer cells were exposed to LS and its effect on proliferation were studied. LS reduced aberrant crypt without affecting tumor pathology. Histological study of colon suggested decrease in numbers of adenomas and lesions. Immunohistochemistry confirmed the antiproliferative activity in adenocarcinomas without affecting the cells of normal colon mucosa. Results on human DLD-1 cells showed LS delayed progression of cell cycle by decreasing expression of cyclin B1 as well as cdk1 by inactivating NF-κB without inducing apoptosis. The study concluded role of LS in suppressing cell proliferation of colon tumors. The suppressive activity on DLD-1 cells was not by apoptosis but by decreased NF-κB activity resulting in suppression of expression levels of cyclin B1 and cdk1.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents, Phytogenic; Azo Compounds; Carcinogens; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Dextran Sulfate; Endoscopy; Humans; Intestinal Mucosa; Naphthoquinones; NF-kappa B; Rats; Signal Transduction

The effects of two naphthoquinones, juglone and plumbagin, and an isocoumarin, hydrangenol, on intestinal carcinogenesis in rats were examined by dietary exposure during the initiation phase. Starting at 5 weeks of age, male F344 rats were fed the diets containing either of the test chemicals at a concentration of 200 ppm or the control diet without the compounds. At 6 weeks of age, all animals were treated with s.c. injections of azoxymethane (AOM) (15 mg/kg body weight, once weekly for 3 weeks) or saline alone. Animals fed experimental diets were changed to the control diet 1 week after the last carcinogen treatment. Animals given plumbagin together with the carcinogen had a lower incidence (41%) and smaller multiplicity (0.48 +/- 0.62) of tumors in the entire intestine compared with those exposed to carcinogen alone (68% and 1.04 +/- 0.62) (P < 0.05 and < 0.01, respectively). The incidence and multiplicity of tumors in the small intestine (7% and 0.07 +/- 0.25) and the multiplicity of tumors in the entire intestine (0.60 +/- 0.76) of animals treated with juglone and the carcinogen were significantly less than those of animals treated with carcinogen alone (P < 0.05 in each). Hydrangenol tended to decrease the incidence and the multiplicity of tumors in the entire intestine induced by AOM, but the effect was not statistically significant. The present data suggest that the naphthoquinones, juglone and plumbagin, could be promising chemopreventive agents for human intestinal neoplasia.

Topics: Animals; Antineoplastic Agents, Phytogenic; Azo Compounds; Benzopyrans; Colonic Neoplasms; Coumarins; Diet; Intestinal Neoplasms; Isocoumarins; Male; Naphthoquinones; Rats; Rats, Inbred F344