Suppression of intestinal carcinogenesis in <i>Apc</i>-mutant mice by limonin

Abstract

Limonoids in citrus fruits are known to possess multiple biological functions, such as anti-proliferative functions in human cancer cell lines. Therefore, we aimed to investigate the suppressive effect of limonin on intestinal polyp development in Apc-mutant Min mice. Five-week-old female Min mice were fed a basal diet or a diet containing 250 or 500 ppm limonin for 8 weeks. The total number of polyps in mice treated with 500 ppm limonin decreased to 74% of the untreated control value. Neoplastic cell proliferation in the polyp parts was assessed by counting PCNA positive cells, and a tendency of reduction was obtained by limonin treatment. Moreover, expression levels of c-Myc and MCP-1 mRNA in the polyp part were reduced by administration of limonin. We finally confirmed the effects of limonin on β-catenin signaling, and found limonin significantly inhibited T-cell factor/lymphocyte enhancer factor-dependent transcriptional activity in a dose-dependent manner in the Caco-2 human colon cancer cell line. Our results suggest that limonin might be a candidate chemopreventive agent against intestinal carcinogenesis.

TRIB3 confers glioma cell stemness via interacting with β‐catenin

“…CSCs are a small number of cells with the ability to self‐renew and proliferate, and are the leading factor for tumor initiation . Microenvironmental stress has been shown to promote the enrichment of cells with stemness . TRIB3 is an important stress‐related gene, which can be induced and upregulated by various stimuli and participate in cell apoptosis, blood sugar and lipid metabolism, adipocyte differentiation, cell stress, and other processes; this hints that TRIB3 could affect CSC progression.…”

The Chemistry and Pharmacology of Citrus Limonoids

“…Das et al [56] further showed that the treatments of IOMM-Lee and CH157MN meningioma cells with (1) can induce apoptosis with enhanced phosphorylation of glycogen synthase kinase 3 β (GSK3β) via inhibition of the Wnt5/β-catenin pathway (EC 50 = 25 µM). While studying the effects of 1 on intestinal polyp from Apc-mutant Min mice, Shimizu et al [54] have observed a reduction of neoplastic cell proliferation after treatment with 1, along with reduced level of expression of c-Myc and MCP-1 mRNA in the polyp part. Moreover, they found that 1 also significantly inhibited T-cell factor/lymphocyte enhancer factor-dependent transcriptional activity in a dose-dependent manner in the Caco-2 human colon cancer cell line.…”

“…The unbalanced solubility profile of the latter may explain the relatively low number of studies on their respective biological activities which are hampered by difficult isolation from natural sources and poor pharmacokinetics. Analgesic [45], anticancer [46][47][48][49][50][51][52][53][54][55][56][57][58][59], anti-inflammatory [45,[60][61][62], antibacterial [63,64], antioxidant [4,65,66], antiviral [67], larvicidal [68,69] Anticancer [46,47,58,59,70], anti-hyperglycemic [71], anti-inflammatory [25,62], antioxidant [4,65,66], antiviral [67], larvicidal [68,69] …”

Dose-response relationship in Schistosoma mansoni juvenile and adult stages following limonin treatment in experimentally infected mice

“…Several biological activities of limonin have been explored such as insecticidal, insect antifeedant, and growthregulating activity on insects as well as antimalarial, antiviral, anticancer, cholesterol-lowering, and antioxidant activities (Kurowska et al 2000a, b;Battinelli et al 2003;Miller et al 2004;Manners 2007;El-Readi et al 2010). It has been shown that limonin exhibits anticancer effects in vitro and suppressive effects on the formation of preneoplastic lesions in vivo (Rahman et al 2015), in addition to its hepatoprotective effects (Mahmoud et al 2014) and anticancer efficacy (Shimizu et al 2015).…”