Eicosanoid signalling pathways in the development and progression of colorectal cancer: novel approaches for prevention/intervention

Abstract

Arachidonic acid metabolism through cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P-450 epoxygenase (EPOX) pathways leads to the generation of biologically active eicosanoids, including prostanoids, leukotrienes, hydroxyeicosatetraenoic acid, epoxyeicosatrienoic acid and hydroperoxyeicosatetraenoic acids. Eicosanoid expression levels vary during tumor development and progression of a range of malignancies, including colorectal cancer. The actions of these autocoids are also directly influenced by diet, as demonstrated by recent evidence for omega-3 fatty acids in colorectal cancer (CRC) prevention and/or treatment. Eicosanoids regulate CRC development and progression, while inhibition of these pathways has generally been shown to inhibit tumor growth/progression. A progressive sequence of colorectal cancer development has been identified, ranging from normal colon, to colitis, dysplasia, and carcinoma. While both COX and LOX inhibition are both promising candidates for colorectal cancer prevention and/or treatment, there is an urgent need to understand the mechanisms through which these signalling pathways mediate their effects on tumorigenesis. This will allow identification of safer, more effective strategies for colorectal cancer prevention and/or treatment. In particular, binding to/signalling through prostanoid receptors have recently been the subject of considerable interest in this area. In this review, we discuss the role of the eicosanoid signalling pathways in the development and progression of colorectal cancer. We discuss the effects of the eicosanoids on tumor cell proliferation, their roles in cell death induction, effects on angiogenesis, migration, invasion and their regulation of the immune response. Signal transduction pathways involved in these processes are also discussed. Finally, novel approaches targeting these arachidonic acid-derived eicosanoids (using pharmacological or natural agents) for chemoprevention and/or treatment of colorectal cancer are outlined.

Potential roles of longan flower and seed extracts for anti-cancer

“…Recent studies have further revealed that some TCMs or their components exhibit anti-tumor activities towards several types of cancer, such as liver [12] , lung [13] , gastric [14] , nasopharyngeal [15] and colorectal cancer [16] . Non-steroidal antiinflammatory drugs have been documented in animal and human studies to reduce the risk of colorectal cancer and adenomatous polyps and have been implicated as a cancer prevention and treatment strategy [1,[17][18][19] . Longan flowers and seeds have been analyzed and were found to possess rich amounts of polyphenols, including proanthocyanidin A2, (-)-epicatechin, gallic acid and ellagic acid, and exhibit strong antioxidant and inflammatory activities [20][21][22][23][24] .…”

Dietary n-3/long-chain n-3 polyunsaturated fatty acids for prevention of sporadic colorectal tumors: A randomized controlled trial in polypectomized participants

“…Human/laboratory studies [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] also suggested that n-3 PUFAs (or omega-3 PUFAs), including alpha-linolenic acid (ALA) and long-chain n-3 PUFAs (LC n-3 PUFAs) (eicosapentaenoic acid [EPA], docosapentaenoic acid [DPA], and docosahexaenoic acid [DHA]) seem to act as anti-tumor promoters in CRC carcinogenesis, like non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin [29][30][31][32][33][34][35][36][37][38]. On the other hand, n-6 PUFAs (or omega-6 PUFAs, mainly linoleic acid (LA)) may act as tumor promoters, because they are upstream chemicals of n-6 family leukotrienes, thromboxanes and prostaglandins, which are catalyzed by lipoxygenase (LOX) and cyclooxygenase (COX) isoenzymes [39][40][41][42][43].…”

“…Because a randomized controlled trial (RCT) is thought to be a high-evidence approach, we planned [46] and conducted a dietary intervention in a polypectomized participant (DIPP) study to elucidate whether n-3 PUFAs or LC n-3 PUFAs may indeed have tumor-suppressive effects. Although recent trials have provided evidence of favorable effects of n-3 PUFAs or LC n-3 PUFAs on the onset of aberrant crypt foci or CRC precursors [25][26][27], RCTs directly exploring long-term effects of n-3 PUFAs or LC n-3 PUFAs on CRTs, to the best of our knowledge, have not been conducted to date. Here, we present the results of our DIPP study.…”

Is there a place for practical chemoprevention of colorectal cancer in light of COX-2 heterogeneity?

“…Arachidonic acid metabolism through cyclooxygenase, lipoxygenase, cytochrome P-450 and epoxygenase leads to overproduction of eicosanoids and plays an important role in the progress of colon neoplasia [16]. Longstanding clinical experience shows that the risk of CRC is statistically lower among people chronically using non-steroidal anti-inflammatory drugs (NSAIDs) [17,18].…”