title: The chemopreventive action of bromelain, from pineapple stem (Ananas comosus L.), on colon carcinogenesis is related to antiproliferative and proapoptotic effects.
abstract: METHODS
  Colorectal cancer is an important health problem across the world. Here, we investigated the possible antiproliferative/proapoptotic effects of bromelain (from the pineapple stem Ananas comosus L., family Bromeliaceae) in a human colorectal carcinoma cell line and its potential chemopreventive effect in a murine model of colon cancer.
  
  
  RESULTS
  Proliferation and apoptosis were evaluated in human colon adenocarcinoma (Caco-2) cells by the (3) H-thymidine incorporation assay and caspase 3/7 activity measurement, respectively. Extracellular signal-related kinase (ERK) and Akt expression were evaluated by Western blot analysis, reactive oxygen species production by a fluorimetric method. In vivo, bromelain was evaluated using the azoxymethane murine model of colon carcinogenesis. Bromelain reduced cell proliferation and promoted apoptosis in Caco-2 cells. The effect of bromelain was associated to downregulation of pERK1/2/total, ERK, and pAkt/Akt expression as well as to reduction of reactive oxygen species production. In vivo, bromelain reduced the development of aberrant crypt foci, polyps, and tumors induced by azoxymethane.
  
  
  CONCLUSIONS
  Bromelain exerts antiproliferative and proapoptotic effects in colorectal carcinoma cells and chemopreventive actions in colon carcinogenesis in vivo. Bromelain-containing foods and/or bromelain itself may represent good candidates for colorectal cancer chemoprevention.
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Romano
authors.forename: Ines
authors.initials: I
authors.lastname: Fasolino
authors.forename: Ester
authors.initials: E
authors.lastname: Pagano
authors.forename: Raffaele
authors.initials: R
authors.lastname: Capasso
authors.forename: Simona
authors.initials: S
authors.lastname: Pace
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Rosa
authors.forename: Natasa
authors.initials: N
authors.lastname: Milic
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Orlando
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Izzo
authors.forename: Francesca
authors.initials: F
authors.lastname: Borrelli
mesh_terms: D031230:Ananas / Q000737:chemistry*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001963:Bromelains / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D008813:Mice, Inbred ICR; D018547:Plant Stems / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D017382:Reactive Oxygen Species; D001963:Bromelains; D053148:Caspase 3; D053179:Caspase 7; C091760:stem bromelain
keywords: Bromelain; Cell proliferation; Chemoprevention; Colon cancer; Protease