Phytate and Butyrate Differently Influence the Proliferation, Apoptosis and Survival Pathways in Human Cancer and Healthy Colonocytes

Lidia Hanna Markiewicz,Wiesław Wiczkowski,Barbara Wróblewska,Anna Maria Ogrodowczyk

doi:10.3390/nu13061887

Lidia Hanna Markiewicz, Wiesław Wiczkowski + Show 2 more

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https://doi.org/10.3390/nu13061887

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Abstract

The colonic epithelium is never exposed to a single factor, therefore studies on the effect of combinations of factors naturally and persistently present in the intestines are of special importance for understanding the phenomena occurring at this place. The aim of the study was to investigate the combined effect of 1 mM phytate and 1 mM butyrate (PA1B1) on cell lines derived from cancer (HCT116 and HT-29) and healthy (NCM460D) human colonic epithelium. Colorimetric and flow cytometry methods were used to determine the proliferation rate, cell cycle, and apoptosis. Selected markers of proliferation, inflammatory, and survival pathways were investigated at the mRNA and/or protein level. The combination of phytate and butyrate disturbed the cell cycle and triggered apoptosis and/or death in both studied cancer colonocytes to a higher extent compared to healthy colonocytes. Moreover, in healthy colonocytes, phytate activated the survival pathway without stimulation of inflammatory response. This may indicate that the response of healthy colonocytes to phytate protects colonic epithelium from the loss of integrity and tightness that would occur if inflammation developed. Based on the obtained results we postulate that studies on both cancer and/or healthy colonocytes should be carried out in the presence of butyrate as the permanent component of colonic contents. This should be of special importance when anti-proliferative/pro-apoptotic activity or inflammatory status of colonocytes is to be investigated.

Highlights

A mixture of 1.0 mM of phytate and 2 mM of butyrate showed the strongest inhibition of cell proliferation up to 50% of the control after 24 h (p ≤ 0.001; Figure 1)
Similar response of NCM460 cells to sulforaphane was reported [43]. These findings suggest that activation of the extracellular signalregulated kinase (ERK) pathway in healthy colonocytes in response to natural substances of pro-apoptotic activity protects colonic epithelium from a loss of integrity and tightness
The combined effect of butyrate and phytate was cell line-specific some cancer cells-specific patterns of response can be indicated. The presence of both factors enhanced their pro-apoptotic effect in cancer cells, while in the healthy ones phytate suppressed the pro-proliferative action of butyrate and activated a pro-survival pathway

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The physiological status of intestinal epithelium is an effect of multiple factors among which diet and intestinal microbiota are the most important ones. Recent reports on the health consequences of particular diet components and nutritional lifestyle shed light on the mutual dependencies of intestinal microbiota and its metabolites, diet, and intestinal epithelium [1,2]. More and more attention is being paid to the dietary plant-derived compounds and their protective effect against civilization diseases at the systemic and cellular level

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