title: Aloe vera non-decolorized whole leaf extract-induced large intestinal tumors in F344 rats share similar molecular pathways with human sporadic colorectal tumors.
abstract: Aloe vera is one of the most commonly used botanicals for various prophylactic and therapeutic purposes. Recently, NTP/NCTR has demonstrated a dose-dependent increase in large intestinal tumors in F344 rats chronically exposed to Aloe barbadensis Miller (Aloe vera) non-decolorized whole leaf extract (AVNWLE) in drinking water. The morphological and molecular pathways of AVNWLE-induced large intestinal tumors in the F344 rats were compared to human colorectal cancer (hCRC) literature. Defined histological criteria were used to compare AVNWLE-induced large intestinal tumors with hCRC. The commonly mutated genes (Kras, Ctnnb1, and Tp53) and altered signaling pathways (MAPK, WNT, and TGF-β) important in hCRC were evaluated within AVNWLE-induced large intestinal tumors. Histological evaluation of the large intestinal tumors indicated eight of twelve adenomas (Ads) and four of twelve carcinomas (Cas). Mutation analysis of eight Ads and four Cas identified point mutations in exons 1 and 2 of the Kras gene (two of eight Ads, two of four Cas), and in exon 2 of the Ctnnb1 gene (three of eight Ads, one of four Cas). No Tp53 (exons 5-8) mutations were found in Ads or Cas. Molecular pathways important in hCRC such as MAPK, WNT, and TGF-β signaling were also altered in AVNWLE-induced Ads and Cas. In conclusion, the AVNWLE-induced large intestinal tumors in F344 rats share several similarities with hCRC at the morphological and molecular levels.
authors.affiliation: Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. pandiriak@niehs.nih.gov
authors.forename: Arun R
authors.initials: AR
authors.lastname: Pandiri
authors.forename: Robert C
authors.initials: RC
authors.lastname: Sills
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Hoenerhoff
authors.forename: Shyamal D
authors.initials: SD
authors.lastname: Peddada
authors.forename: Thai-Vu T
authors.initials: TV
authors.lastname: Ton
authors.forename: Hue-Hua L
authors.initials: HH
authors.lastname: Hong
authors.forename: Gordon P
authors.initials: GP
authors.lastname: Flake
authors.forename: David E
authors.initials: DE
authors.lastname: Malarkey
authors.forename: Greg R
authors.initials: GR
authors.lastname: Olson
authors.forename: Igor P
authors.initials: IP
authors.lastname: Pogribny
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Walker
authors.forename: Mary D
authors.initials: MD
authors.lastname: Boudreau
mesh_terms: D000236:Adenoma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D000504:Aloe / Q000737:chemistry*; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D006651:Histocytochemistry; D006801:Humans; D007414:Intestinal Neoplasms / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D007420:Intestine, Large / Q000473:pathology; D010936:Plant Extracts / Q000633:toxicity*; D018515:Plant Leaves / Q000737:chemistry; D025341:Principal Component Analysis; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D014408:Biomarkers, Tumor; D010936:Plant Extracts