Oral Administration of Microencapsulated B. Longum BAA-999 and Lycopene Modulates IGF-1/IGF-1R/IGFBP3 Protein Expressions in a Colorectal Murine Model

Abstract

The Insulin-like growth factor-I/Insulin-like growth factor-I receptor (IGF-1/IGF-1R) system is a major determinant in colorectal cancer (CRC) pathogenesis. Probiotics (Bifidobacterium longum, BF) and lycopene (LYC) have been individually researched for their beneficial effects in the prevention of CRC. However, the effect of a combined treatment of microencapsulated BF and LYC on IGF-1/IGF-1R/IGFBPs (Insulin-like growth factor-binding proteins) expression in an azoxymethane (AOM)-dextran sulfate sodium (DSS)-induced CRC model have not been demonstrated. BF was microencapsulated by the spray drying technique, with high viability, and daily gavaged with LYC for 16 weeks to CD-1 mice in an AOM-DSS model. The results indicated that BF- and BF + LYC-treated groups had significantly lower inflammation grade, tumor incidence (13–38%) and adenocarcinoma (13–14%) incidence compared to the AOM + DSS group (80%), whereas LYC treatment only protected against inflammation grade and incidence. Caecal, colonic and fecal pH and β-glucuronidase (β-GA) values were significantly normalized by BF and LYC. Similarly, BF and BF + LYC treatments significantly reduced both the positive rate and expression grade of IGF-1 and IGF-1R proteins and normalized Insulin-like growth factor-binding protein-3 (IGFBP3) expression. Based on intestinal parameters related to the specific colon carcinogenesis in an AOM-DSS-induced model, LYC and microencapsulated BF supplementation resulted in a significant chemopreventive potential through the modulation of IGF-1/IGF-1R system.

Chemopreventive Effect of the Germinated Oat and Its Phenolic-AVA Extract in Azoxymethane/Dextran Sulfate Sodium (AOM/DSS) Model of Colon Carcinogenesis in Mice

“…In addition, DSS causes bloody diarrhea, ulcerations, and heavy infiltration of inflammatory cells into the mucosa [62], suggesting that inflammation is involved in the tumor-promotion activity of DSS. Similar results have been observed in our study and by others in the AOM/DSS-induced CRC mouse model [38][39][40]63,64].…”

“…As we previously reported, increased β-GA and pH values have been related to the carcinogenic effect of the AOM in the presence of DSS [38]. Therefore, β-GA and pH values in fecal, cecal, and colonic samples collected before and during the euthanizing of the animals were also determined, and the results are shown in Table 2.…”

New Insights into Molecular Mechanism behind Anti-Cancer Activities of Lycopene

“…Similarly, for high dosage, there was a significant spike in positive rates of IGF-1, IGF-2 and IGFBP3 despite a significant reduction in IGFBP2. There was no change in the number of tumors or adenocarcinomas incidence but there was noticeable focal necrosis present in colonic tissue [79]. The anti-cancer effect of lycopene in this experiment could be said to be moderate as there were both positive and negative outcomes, accompanied by its ineffectiveness in reducing the number of tumors and adenocarcinomas incidence.…”

Effect of Lycopene on Oral Squamous Cell Carcinoma Cell Growth by Inhibiting IGF1 Pathway

“…Notably, previous research has shown that lycopene intake increases serum total IGFBP3 concentrations in clinical trials and basic research. 27 , 28 The presence and abnormal expression of pro-inflammatory gene, such as FOXO1 in the tumor microenvironment is consistent event within a maladjustment of chronic cellular immune response. 29 , 30 It is identical to this study.…”