Luteolin inhibits cell proliferation during Azoxymethane-induced experimental colon carcinogenesis via Wnt/ β-catenin pathway.
The protective role of Luteolin (LUT) against Azoxymethane (AOM)-induced mouse colon carcinogenesis has been documented earlier. The aim of this study is to investigate on the mechanism of chemopreventive action exhibited by LUT employing AOM-induced colon carcinogenesis in mice as an experimental model. LUT inhibited AOM-induced colon tumorigenesis by decreasing tumor incidence and size. LUT reduced the cell proliferation by decreasing the number of Argyrophillic nucleolar organizer region (AgNOR)/nucleus and Proliferating Cell Nuclear Antigen (PCNA) index. It was known that β-catenin is a key effector in Wingless and Int (Wnt) signaling pathway and 90% of colon tumors arise from mutations in this pathway. In this study, we show evidence that LUT inhibited colon carcinogenesis by decreasing AOM-induced cell proliferation through the involvement of β-catenin, Glycogen synthase kinase (GSK)-3β and cyclin D1, the key components in Wnt signaling pathway. In conclusion, the protective effect of LUT could be attributed to inhibition of AOM-induced cellular proliferation probably through the involvement of β-catenin, GSK-3β and cyclin D1.
Ashokkumar
Pandurangan
P
Department of Biochemistry, University of Madras, Guindy campus, Chennai, Tamil Nadu, India.
Sudhandiran
Ganapasam
G
D000818:Animals; D001397:Azoxymethane; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D047311:Luteolin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011073:Polyamines / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D016622:Silver Staining; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D011073:Polyamines; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D051153:Wnt Proteins; D051176:beta Catenin; D019938:Cyclin D1; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D047311:Luteolin; D001397:Azoxymethane