title: Lawsone suppresses azoxymethane mediated colon cancer in rats and reduces proliferation of DLD-1 cells via NF-κB pathway.
abstract: 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.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of PLA General Hospital, Beijing 100048, China. Electronic address: wyuaeo@163.com.
authors.forename: Shi-Bin
authors.initials: SB
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Beijing Anzhen Hospital,Capital Medical University, Beijing 100029, China. Electronic address: tpvndz@163.com.
authors.forename: Zhenzhou
authors.initials: Z
authors.lastname: Tao
authors.affiliation: Department of Gastroenterology, The First People's Hospital of Qujing, Qujing, Yunnan Province, 655000, China. Electronic address: liping582@hotmail.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001391:Azo Compounds; D002273:Carcinogens; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D016264:Dextran Sulfate; D004724:Endoscopy; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D016328:NF-kappa B / Q000187:drug effects*; D009285:Naphthoquinones / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001391:Azo Compounds; D002273:Carcinogens; D016328:NF-kappa B; D009285:Naphthoquinones; C001825:azomethane; D016264:Dextran Sulfate; C005090:lawsone
keywords: Colon cancer; DLD-1 cells; Endoscopy; KAD rats; Lawsone