The chemopreventive action of bromelain, from pineapple stem (Ananas comosus L.), on colon carcinogenesis is related to antiproliferative and proapoptotic effects

Mol Nutr Food Res. 2014 Mar;58(3):457-65. doi: 10.1002/mnfr.201300345. Epub 2013 Oct 1.

Abstract

Scope: 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.

Methods and 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.

Conclusion: 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.

Keywords: Bromelain; Cell proliferation; Chemoprevention; Colon cancer; Protease.

MeSH terms

  • Ananas / chemistry*
  • Animals
  • Anticarcinogenic Agents / pharmacology
  • Apoptosis / drug effects
  • Bromelains / pharmacology*
  • Caspase 3 / metabolism
  • Caspase 7 / metabolism
  • Cell Line, Tumor / drug effects
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / prevention & control*
  • Drug Screening Assays, Antitumor
  • Humans
  • Male
  • Mice, Inbred ICR
  • Plant Stems / chemistry
  • Reactive Oxygen Species / metabolism

Substances

  • Anticarcinogenic Agents
  • Reactive Oxygen Species
  • Bromelains
  • Caspase 3
  • Caspase 7
  • stem bromelain