Diet-Derived Phytochemicals Targeting Colon Cancer Stem Cells and Microbiota in Colorectal Cancer

Abstract

Colorectal cancer (CRC) is a fatal disease caused by the uncontrolled propagation and endurance of atypical colon cells. A person's lifestyle and eating pattern have significant impacts on the CRC in a positive and/or negative way. Diet-derived phytochemicals modulate the microbiome as well as targeting colon cancer stem cells (CSCs) that are found to offer significant protective effects against CRC, which were organized in an appropriate spot on the paper. All information on dietary phytochemicals, gut microbiome, CSCs, and their influence on CRC were accessed from the various databases and electronic search engines. The effectiveness of CRC can be reduced using various dietary phytochemicals or modulating microbiome that reduces or inverses the progression of a tumor as well as CSCs, which could be a promising and efficient way to reduce the burden of CRC. Phytochemicals with modulation of gut microbiome continue to be auspicious investigations in CRC through noticeable anti-tumorigenic effects and goals to CSCs, which provides new openings for cancer inhibition and treatment.

Keywords: CRC therapy; colon cancer stem cells; gut microbiota; phytochemicals.

Figure 1

Renewal and differentiation of cancer stem cells (CSC). Diet-derived phytochemicals generally attenuate various signaling mediated renewal and differentiation and thereby regulate CSC proliferation.

Figure 2

Various in vitro and in vivo studies showed the phytochemicals inhibit cell propagation, differentiation, angiogenesis, and anti-apoptotic activities in the colon. Abbreviation: Akt- serine/threonine-specific protein kinase; AP1—Activator protein 1; ASK1—apoptosis signal-regulating kinase 1; Bax—bcl-2-like protein; Bcl 2-B-cell lymphoma 2; Bid—BH3 Interacting Domain Death Agonist; CIP1/waf1—cyclin-dependent kinase inhibitor 1; Cyt C—cytochrome C; DNMT—DNA methyltransferase; EGFR—epidermal growth factor receptor; FAK—Focal adhesion kinase; GSK3- glycogen synthase kinase-3; HAT—histone acetyltransferases; HDAC—histone deacetylase; IL- interleukin; JNK—c-Jun N-terminal kinases; Kip1—kinesin-like protein1; MKK4—mitogen-activated protein kinase kinase 4; NF-κB—nuclear factor kappa-B; PDGF—platelet-derived growth factor; PDGFRα—platelet-derived growth factor receptor A; PI3K—Phosphoinositide 3-kinases; SrC—protooncogene c; STAT3—signal transducer and activator of transcription 3; TGFα—Transforming Growth Factor-alpha; VEGF—vascular endothelial growth factor; VEGFR—vascular endothelial growth factor receptor.

Figure 3

Effect of the gut microbiome on colon cancer stemm cells (CSCs) and colorectal cancer (CRC).

Figure 4

Dysbiosis of gut microbiota causes a high risk of colorectal cancer (CRC).

Figure 5

Diet-derived phytochemicals stabilize the microbiome status (Eubiosis) that inhibits Wnt/β-catenin signaling pathways successively prevent intestinal infection and inflammation.

Figure 6

Triangular relationship between phytochemicals, gut microbiome, and cancer stem cells (CSCs).