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