title: Prevention of azoxymethane/dextran sodium sulfate-induced mouse colon carcinogenesis by processed Aloe vera gel.
abstract: The preventive effect of a processed Aloe vera gel (PAG) on colon carcinogenesis was examined using an azoxymethane (AOM)-initiated and dextran sodium sulfate (DSS)-promoted mouse colon carcinogenesis model. Oral administration of PAG (200, or 400mg/kg/day) significantly reduced the multiplicity of colonic adenomas and adenocarcinomas compared with the AOM/DSS only-treated mice. In the mice treated with 400mg/kg of PAG, adenoma and adenocarcinoma development was reduced to 80% and 60%, respectively, compared to 100% in the PAG-untreated AOM/DSS-treated mice. Western blot analysis using colon extracts showed that PAG reduced the activation of nuclear factor kappa B (NF-κB), resulting in the inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression. PAG appeared to inhibit the NF-κB activation through the activation of peroxisome proliferator-activated receptor gamma. PAG also inhibited the expression and phosphorylation of signal transducer and activator of transcription 3, which is known to connect inflammation and cancer. In addition, PAG inhibited cell cycle progression-inducing cellular factors, such as extracellular signal-regulated kinases 1/2, cyclin-dependent kinase 4, and cyclin D1. On the other hand, PAG increased the expression of Caudal-related homeobox transcription factor 2, which is known to be a tumor suppressor in colorectal cancer. These findings show that PAG suppresses colitis-related colon carcinogenesis by inhibiting both chronic inflammation and cell cycle progression in the colon.
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju 28644, South Korea.
authors.forename: Sun-A
authors.initials: SA
authors.lastname: Im
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju 28644, South Korea.
authors.forename: Ji-Wan
authors.initials: JW
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju 28644, South Korea.
authors.forename: Hee-Suk
authors.initials: HS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju 28644, South Korea.
authors.forename: Chan-Su
authors.initials: CS
authors.lastname: Park
authors.affiliation: Univera Inc., Seoul 04782, South Korea.
authors.forename: Eunju
authors.initials: E
authors.lastname: Shin
authors.affiliation: Univera Inc., Seoul 04782, South Korea.
authors.forename: Seon-Gil
authors.initials: SG
authors.lastname: Do
authors.affiliation: College of Pharmacy, Korea University, Sejong 30019, South Korea.
authors.forename: Young In
authors.initials: YI
authors.lastname: Park
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju 28644, South Korea. Electronic address: cklee@chungbuk.ac.kr.
authors.forename: Chong-Kil
authors.initials: CK
authors.lastname: Lee
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D000504:Aloe; D000818:Animals; D001397:Azoxymethane; D000071616:CDX2 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D063646:Carcinogenesis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000150:complications*; D015179:Colorectal Neoplasms / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005260:Female; D005782:Gels / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000627:therapeutic use*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000071616:CDX2 Transcription Factor; C487514:Cdx2 protein, mouse; D005782:Gels; D016328:NF-kappa B; D010936:Plant Extracts; D025521:Tumor Suppressor Proteins; D016264:Dextran Sulfate; D001397:Azoxymethane
keywords: Cell cycle progression; Chronic inflammation; Colon carcinogenesis; Myeloid-derived suppressor cells; Processed Aloe vera gel