Phytochemicals and Gastrointestinal Cancer: Cellular Mechanisms and Effects to Change Cancer Progression

Abstract

Gastrointestinal (GI) cancer is a prevailing global health disease with a high incidence rate which varies by region. It is a huge economic burden on health care providers. GI cancer affects different organs in the body such as the gastric organs, colon, esophagus, intestine, and pancreas. Internal and external factors like smoking, obesity, urbanization, genetic mutations, and prevalence of Helicobacter pylori and Hepatitis B and Hepatitis C viral infections could increase the risk of GI cancer. Phytochemicals are non-nutritive bioactive secondary compounds abundantly found in fruits, grains, and vegetables. Consumption of phytochemicals may protect against chronic diseases like cardiovascular disease, neurodegenerative disease, and cancer. Multiple studies have assessed the chemoprotective effect of selected phytochemicals in GI cancer, offering support to their potential towards reducing the pathogenesis of the disease. The aim of this review was to summarize the current knowledge addressing the anti-cancerous effects of selected dietary phytochemicals on GI cancer and their molecular activities on selected mechanisms, i.e., nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), detoxification enzymes, adenosine monophosphate activated protein kinase (AMPK), wingless-related integration site/β-catenin (wingless-related integration site (Wnt) β-catenin, cell apoptosis, phosphoinositide 3-kinases (PI3K)/ protein kinase B AKT/ mammalian target of rapamycin (mTOR), and mitogen-activated protein kinase (MAPK). In this review phytochemicals were classified into four main categories: (i) carotenoids, including lutein, lycopene, and β-carotene; (ii) proanthocyanidins, including quercetin and ellagic acid; (iii) organosulfur compounds, including allicin, allyl propyl disulphide, asparagusic acid, and sulforaphane; and (iv) other phytochemicals including pectin, curcumins, p-coumaric acid and ferulic acid. Overall, phytochemicals improve cancer prognosis through the downregulation of β-catenin phosphorylation, therefore enhancing apoptosis, and upregulation of the AMPK pathway, which supports cellular homeostasis. Nevertheless, more studies are needed to provide a better understanding of the mechanism of cancer treatment using phytochemicals and possible side effects associated with this approach.

Keywords: anti-cancerous effects; apoptosis; gastrointestinal cancer; intestinal cancer; phytochemical.

Figure 1

Schematic illustration of seven selected mechanisms modulated by GI cancer. The figure is divided into seven columns and three rows. The column headings represent the pathways while the row headings represent target genes/proteins for each pathway (blue), the overview physiological effect of these genes on pathways (dark yellow), and changes occurring on these pathways modulated by GI cancer.

Figure 2

Phytochemicals as anti-GI cancer agents: mode(s) of action, aberrant signaling pathways (Wnt/β-catenin, detoxification enzymes, cellular apoptosis, PI3K/AKT/mTOR, AMPK, MAPK, and NF-κB), and pathway components targeted by phytochemicals (highlighted in green). Phytochemicals have a wide range of anti-cancerous actions through which one could target multiple mechanisms. These phytochemicals can enhance or suppress (green and red lines, respectively) the mechanisms through several activities. (see text for detailed mode(s) of action for phytochemicals mentioned).