Luteolin inhibits cell proliferation during Azoxymethane-induced experimental colon carcinogenesis via Wnt/ β-catenin pathway

Abstract

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.

Effect of Luteolin on the Levels of Glycoproteins During Azoxymethane-induced Colon Carcinogenesis in Mice

“…Carbohydrates moieties of glycoproteins have also been implicated in the transport of metabolites across cell membranes and also observed a direct relationship between glycoproteins and tumorigenesis (Femia et al, 2004). Previous studies from our laboratory, showed LUT decreases the incidence of aberrant crypt foci (Ashokkumar & Sudhandiran, 2008), reduces the tumor formation and inhibits the cell proliferation via Wnt/β-catenin mediated pathway (Ashokkumar & Sudhandiran, 2011) In the present study, evaluates the modulating effect of LUT on MDF, glycoconjugates and lipid peroxidation in AOM-induced colon cancer.…”

Signal Transducer and Activator of Transcription 3 - A Promising Target in Colitis-Associated Cancer

“…In addition, AOM-induced CRC appears to follow the concept in which tumor initiation is followed by tumor promotion and progression in a sequential manner. Specifically, AOM induces the onset of ACF, as the precursor lesion and Mucin depleted foci (Ashokkumar and Sudhandiran, 2008;Norazalina et al, 2010;Pandurangan et al, 2012) followed by the onset of adenocarcinoma (Ashokkumar and Sudhandiran, 2011;Shafie et al, 2013) most often of the distal colon, and, finally, metastasis to mesenteric lymph nodes and liver (Reddy, 2004).…”

“…The expression of β-catenin was downregulated by some chemopreventive agents during chemically induced CRC and in vitro (Ashokkumar and Sudhandiran, 2011;Kaur et al, 2010;Shafie et al, 2013). Aberrant activation of both STAT3 and Wnt/β-catenin (Figure 2) often occurs in malignancies, and the two pathways regulate each other in different cancer cell lines (Armanious et al, 2010;Kawada et al, 2006;Yan et al, 2008).…”

Dietary Non-nutritive Factors in Targeting of Regulatory Molecules in Colorectal Cancer: An Update

“…1, 2 Dimethyl hydrazine and azoxymethane (AOM) are frequently used to induce colon cancer in rodents (Prabhu et al, 2009;Norazalina et al, 2010;Nurul-Husna et al, 2010;Ashokkumar and Sudhandiran, 2011). The spectrum of AOM-induced epithelial lesions resembles those of the various types of neoplastic lesions in human CRC.…”

“…Chemopreventive agents such as Polymeric Black Tea (Patel et al, 2008) and Luteolin (Ashokkumar and Sudhandiran, 2011) both targets wnt/β-catenin pathway. Sphingadiene is a derivative of sphigolipid inhibits colon cancer by downregulating wnt/β-catenin pathway (Kumar et al, 2013).…”