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World J Gastrointest Oncol. Jan 15, 2014; 6(1): 1-10
Published online Jan 15, 2014. doi: 10.4251/wjgo.v6.i1.1
Approaches that ascertain the role of dietary compounds in colonic cancer cells
Michael Bordonaro, Koen Venema, Adeline K Putri, Darina Lazarova
Michael Bordonaro, Department of Basic Sciences, The Commonwealth Medical College, Scranton, PA 18509, United States
Koen Venema, TNO, Research group Kinetics Research for Food and Pharma, Zeist 3700 AJ, The Netherlands
Adeline K Putri, Maastricht University, Health Food Innovation Management, Campus Venlo, Venlo 5911 AA, The Netherlands
Darina Lazarova, Department of Basic Sciences, The Commonwealth Medical College, Scranton, PA 18509, United States
Supported by NIH grants Acknowledges the Support of the European Science Foundation, in the framework of the Research Networking Program, No. R15CA152852-01; The European Network for Gastrointestinal Health Research, No. R15CA149589-01
Author contributions: All authors contributed equally to this work.
Correspondence to: Darina Lazarova, PhD, Associate Professor, Department of Basic Sciences, The Commonwealth Medical College, 525 Pine Street, Scranton, PA 18509, United States.
Telephone: +1-57-5049645 Fax: +1-57-5049636
Received: October 4, 2013
Revised: November 26, 2013
Accepted: December 17, 2013
Published online: January 15, 2014

Preventive approaches against cancer have not been fully developed and applied. For example, the incidence of some types of cancer, including colon cancer, is highly dependent upon lifestyle, and therefore, amenable to prevention. Among the lifestyle factors, diet strongly affects the incidence of colon cancer; however, there are no definitive dietary recommendations that protect against this malignancy. The association between diet-derived bioactives and development of colonic neoplasms will remain ill defined if we do not take into account: (1) the identity of the metabolites present in the colonic lumen; (2) their concentrations in the colon; and (3) the effect of the colonic contents on the function of individual bioactives. We review two approaches that address these questions: the use of fecal water and in vitro models of the human colon. Compared to treatment with individual diet-derived compounds, the exposure of colon cancer cells to samples from fecal water or human colon simulators mimics closer the in vitro conditions and allows for more reliable studies on the effects of diet on colon cancer development. The rationale and the advantages of these strategies are discussed from the perspective of a specific question on how to analyze the combined effect of two types of bioactives, butyrate and polyphenol metabolites, on colon cancer cells.

Keywords: Human colon model, Fecal water, Diet, Colon cancer, Prevention, Butyrate, Polyphenols, WNT signaling

Core tip: Studies on diet and colorectal cancer are in their infancy, and the relevance of many publications on the topic is questionable due to three problems: (1) there is uncertainty about which diet-derived compounds are present in the colon; (2) most studies have focused on individual bioactives; whereas, food intake results in complex metabolite mixtures; and (3) the physiological concentrations of many colonic bioactives are unknown. Here we discuss how the use of fecal water samples and in vitro models of human colon address these problems.