Page 39 - Read Online

bowel diseases, such as ulcerative colitis and Crohn’s colorectal CSCs. Further understanding of the molecular
disease. [81,82] A recent study showed that the inflammatory mechanisms underlying the regulation of CSC properties
lipid mediators leukotriene D4 and PGE2 increased the by environmental factors may lead to the development of
ALDH+ cell population, colony formation capacity, and potential therapeutic targets for patients with CRC.
tumor growth in a xenograft model of colon cancer. [83]
Financial support and sponsorship
A high-fat diet can cause changes in the composition Nil.
of the intestinal microbiota, and affect gut immune
and infl ammatory effectors implicated in intestinal Confl icts of interest
tumorigenesis. [84-86] In contrast, omega-3 polyunsaturated There are no confl icts of interest.
fatty acids (PUFAs) have shown substantial benefi ts
in patients with the chronic infl ammatory disease. References
In a placebo-controlled, randomized controlled
trial, administration of omega-3 PUFAs decreased 1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J,
polyp number, size, and overall burden in patients Jemal A. Global cancer statistics, 2012. CA Cancer J Clin
2015;65:87-108.
with familial adenomatous polyposis. Omega-3 2. Stewart BW, Wild CP. World Cancer Report 2014. Geneva:
[87]
PUFAs were shown to inhibit proliferation and World Health Organization; 2014.
angiogenesis, and exert a pro-apoptotic effect in 3. Akin H, Tozun N. Diet, microbiota, and colorectal cancer.
several in vitro models of CRC. [88-91] One possible J Clin Gastroenterol 2014;48 Suppl 1:S67-9.
molecular mechanism involves the G-protein-coupled 4. Bardou M, Barkun AN, Martel M. Obesity and colorectal
receptor 120, which functions as an omega-3 fatty cancer. Gut 2013;62:933-47.
acid receptor/sensor in pro-infl ammatory macrophages 5. Song L, Li Y, He B, Gong Y. Development of Small Molecules
and mature adipocytes and represses the production Targeting the Wnt Signaling Pathway in Cancer Stem Cells for
the Treatment of Colorectal Cancer. Clin Colorectal Cancer
of TNF and IL-6, as well as macrophage-induced 2015. doi: 10.1016/j.clcc.2015.02.001.
tissue infl ammation. [92,93] Furthermore, omega-3 PUFAs 6. Terzic J, Grivennikov S, Karin E, Karin M. Infl ammation and
down-regulated the expression of CRC stem-like colon cancer. Gastroenterology 2010;138:2101-14.e5.
cell marker CD133, and up-regulated the colorectal 7. Li R, Grimm SA, Chrysovergis K, Kosak J, Wang X, Du Y,
epithelium differentiation markers cytokeratin 20 and Burkholder A, Janardhan K, Mav D, Shah R, Eling TE,
[94]
mucin 2. A recent study revealed that the low-cytotoxic Wade PA. Obesity, rather than diet, drives epigenomic
combination of eicosapentaenoic acid-free fatty acid, alterations in colonic epithelium resembling cancer
progression. Cell Metab 2014;19:702-11.
epigallocatechin-3-gallate, and grape-seed extract (GSE) 8. Aleksandrova K, Boeing H, Jenab M, Bueno-de-Mesquita HB,
inhibited mammalian target of rapamycin signaling and Jansen E, van Duijnhoven FJ, Fedirko V, Rinaldi S, Romieu I,
thus reduced cell proliferation and induced apoptosis in Riboli E, Romaguera D, Westphal S, Overvad K, Tjonneland A,
[95]
CRC cells. GSE pre-treatment of adipocytes decreased Boutron-Ruault MC, Clavel-Chapelon F, Kaaks R, Lukanova A,
their growth-promoting effects on CRC cells. In addition, Trichopoulou A, Lagiou P, Trichopoulos D, Agnoli C,
adipocyte-conditioned media collected after chronic Mattiello A, Saieva C, Vineis P, Tumino R, Peeters PH,
and acute pre-treatment with GSE signifi cantly reduced Arguelles M, Bonet C, Sanchez MJ, Dorronsoro M, Huerta JM,
Barricarte A, Palmqvist R, Hallmans G, Khaw KT, Wareham N,
the chemotactic properties of adipocytes toward CRC Allen NE, Crowe FL, Pischon T. Total and high-molecular
cell invasion. Finally, GSE decreased the expression of weight adiponectin and risk of colorectal cancer: the European
CD44 and inhibited adipocyte-mediated pro-tumorigenic Prospective Investigation into Cancer and Nutrition Study.
signals in CSC-enriched colonospheres. Overall, Carcinogenesis 2012;33:1211-8.
[96]
these fi ndings indicate a close link between obesity 9. Wong HL, Koh WP, Probst-Hensch NM, Van den Berg D,
and chronic infl ammation, leading to CRC progression Yu MC, Ingles SA. Insulin-like growth factor-1 promoter
polymorphisms and colorectal cancer: a functional genomics
through enhanced colorectal CSC properties, whereas approach. Gut 2008;57:1090-6.
some nutrients decrease the expression of CSC markers 10. Ochs-Balcom HM, Cicek MS, Thompson CL, Tucker TC,
and attenuate the properties of CSCs. Elston RC, Plummer SJ, Casey G, Li L. Association of
vitamin D receptor gene variants, adiposity and colon cancer.
Conclusion Carcinogenesis 2008;29:1788-93.
11. Brink M, Weijenberg MP, De Goeij AF, Schouten LJ,
The microenvironment surrounding cancer cells forms Koedijk FD, Roemen GM, Lentjes MH, De Bruine AP,
the CSC niche, allowing them to give rise to a hierarchy Goldbohm RA, Van Den Brandt PA. Fat and K-ras mutations
of proliferative and differentiating cells. Targeting the in sporadic colorectal cancer in The Netherlands Cohort Study.
innate pathways and molecules between colorectal Carcinogenesis 2004;25:1619-28.
CSCs and their environment may thus represent a 12. Guina T, Biasi F, Calfapietra S, Nano M, Poli G.
promising therapeutic strategy, and may provide a Infl ammatory and redox reactions in colorectal carcinogenesis.
complementary approach to conventional therapies that Ann N Y Acad Sci 2015;1340:95-103.
target the malignant cells themselves. Anti-tumorigenic 13. Yang X, Zhang F, Wang Y, Cai M, Wang Q, Guo Q, Li Z,
Hu R. Oroxylin A inhibits colitis-associated carcinogenesis
agents related to nutrients in the microenvironment may through modulating the IL-6/STAT3 signaling pathway.
have particular potential to eliminate the population of Infl amm Bowel Dis 2013;19:1990-2000.
Journal of Cancer Metastasis and Treatment ¦ Volume 1 ¦ Issue 3 ¦ October 15, 2015 ¦ 159