Processed Aloe vera gel inhibits colitis-related colon carcinogenesis by inhibiting both chronic inflammation and cell cycle progression in the colon

Abstract

The processed Aloe vera gel (PAG) contains immunomodulatory polysaccharides, which consists of a mixture of polymer chains of b-(1,4)-linked acetylated galactomannan with different lengths. PAG was shown to inhibit azoxymethane(AOM)-initiated and dextran sodium sulfate(DSS)-promoted colon carcinogenesis model in mice. In the present study, we examined the molecular mechanisms for the inhibition of colitis-associated colon carcinogenesis by PAG. PAG administration significantly inhibited the production of pro-inflammatory cytokines and mediators in the colon. Western blot analysis using the colon extracts showed that PAG administration reduced the activation of NF-kB resulting in the inhibition of iNOS and COX-2 expression. PAG appeared to inhibit NF-kB activation through the PPARγ activation. PAG administration also inhibited the expression and phosphorylation of STAT3, which was known to connect inflammation and cancer. PAG administration also inhibited cell cycle progression-related transcription factors such as the proliferating cell nuclear antigen (PCNA), ERK, cyclin-dependent kinase (CDK) 4 and cyclin D1. In contrast, PAG administration increased the expression of CDX2, which was known to be a tumor suppressor in colorectal cancers. These findings show that PAG suppresses colitis-related colon carcinogenesis by inhibiting both chronic inflammation and cell cycle progression in the colon.