title: Anti-inflammatory and proapoptotic effects of umbelliferone in colon carcinogenesis.
abstract: Colorectal cancer (CRC) is a serious health problem throughout the world. 5-Flurouracil, the first-line chemotherapy of colorectal cancer often produces more toxicity to neighboring cells; however, it is still used for CRC treatment. To overcome this, umbelliferone (UMB), a less toxic bioflavonoid has been used to test its anticancer effects on animal model. The objective of the present study is to evaluate the anticancer activity of UMB on 1,2-dimethylhydrazine (DMH)-induced rat colon tumorigenesis to determine the development of aberrant crypt foci (ACF), agyrophylic nucleolar organizer regions (AgNORs), mast cell recruitment, pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and also study the expressions of inducible nitric oxide synthase, cyclooxygenase (COX)-2, and apoptotic markers. DMH-induced rats showed increased ACF number (incidence), multiplicity and its distribution, counts of AgNORs, mast cells, inflammatory markers and apoptotic proteins. Interestingly, UMB supplementation to DMH-induced rats (group 4) significantly (p < 0.05) suppressed ACF development, AgNORs, mast cells, and inflammatory markers and increased the apoptotic markers as compared to DMH-induced rats (group 2). We concluded that UMB is a potential anticancer agent that can be used for the prevention and treatment of CRC.
authors.affiliation: Department of Biochemistry, Periyar University, Salem, Tamil Nadu, India.
authors.forename: R
authors.initials: R
authors.lastname: Muthu
authors.affiliation: Department of Biochemistry, Periyar University, Salem, Tamil Nadu, India.
authors.forename: N
authors.initials: N
authors.lastname: Selvaraj
authors.affiliation: Department of Biochemistry, Periyar University, Salem, Tamil Nadu, India manjucb11@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Vaiyapuri
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000633:toxicity; D058739:Aberrant Crypt Foci / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D034961:Antigens, Nuclear / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology; D017208:Rats, Wistar; D014468:Umbelliferones / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D034961:Antigens, Nuclear; D000972:Antineoplastic Agents, Phytogenic; D016207:Cytokines; D014468:Umbelliferones; C051963:nucleolar organizer region associated proteins; C031477:7-hydroxycoumarin; D019813:1,2-Dimethylhydrazine
keywords: COX-2; Colon cancer; aberrant crypt foci; iNOS; umbelliferone