Nutraceuticals as potential therapeutic agents for colon cancer: a review

Abstract

Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting both men and women. The modern diet and lifestyles, with high meat consumption and excessive alcohol use, along with limited physical activity has led to an increasing mortality rate for colon cancer worldwide. As a result, there is a need to develop novel and environmentally benign drug therapies for colon cancer. Currently, nutraceuticals play an increasingly important role in the treatment of various chronic diseases such as colon cancer, diabetes and Alzheimer׳s disease. Nutraceuticals are derived from various natural sources such as medicinal plants, marine organisms, vegetables and fruits. Nutraceuticals have shown the potential to reduce the risk of colon cancer and slow its progression. These dietary substances target different molecular aspects of colon cancer development. Accordingly, this review briefly discusses the medicinal importance of nutraceuticals and their ability to reduce the risk of colorectal carcinogenesis.

Keywords: 5-FU, 5-fluorouracil; ACC, acetyl CoA carboxylase; ACF, aberrant crypt foci; ACL, ATP-citrate lyase; ASTX, astaxanthin; COX-2, cyclooxygenase 2; Colon cancer; DHA, decahexaenoic acid; DMH, 1,2-dimethylhydrazine; DR, death receptor; EGCG, epigallocatechingallate; EPA, eicosapentaenoic acid; FAS, fatty acid synthase; GADD, growth arrest and DNA damage; HMG-CoA, 3-hydroxy-3-methyl-glutaryl CoA; HUVEC, human umbilical vein endothelial cell; IGF, insulin-like growth factor; IL, interleukin; LDH, lactate dehydrogenase; MMP, matrix metallo-proteins; Marine organisms; NF-κB, nuclear factor-kappa B; Nutraceuticals; PRAP, prolactin receptor associated protein; Plant derivatives; TCA, tricarboxylic acid cycle; TNF, tumor necrosis factor; TRAIL, tumor necrosis factor-related apoptosis-induced ligand; Therapeutics; VEGF, vascular endothelial growth factor.

Graphical abstract

Figure 1

Different classes of nutraceuticals and their uses.

Figure 2

The mortality and incidence rate of colon cancer in the years 2002–2012.

Figure 3

Biochemical metabolic response of colon cancer cells. The proposed mechanism of colorectal tumorigenesis: MDH, malate dehydrogenase; PHD, prolyl hydroxylase; HRE, hypoxia-responsive element; FIH-1, factor inhibiting HIF-1; TAD-C, C-terminal transcriptional activation domain; UGP2, UDP-glucose pyrophosphorylase 2; GSK3, glycogen synthetase kinase 3; ECM, extracellular matrix; pVHL, von Hippel–Lindau protein; TCA, tricarboxylic acid. Red upward pointing arrows and green downward pointing arrows denote the up-regulation and down-regulation of enzymes of metabolic pathways, respectively. All altered proteins found in the present study are highlighted as follows: up-regulated proteins are in red, and down-regulated proteins are in blue.

Figure 4

Structures of clinically important secondary metabolite used in colon cancer treatment.