Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Dec;51(6):512-9.

Phospholipid remodeling and eicosanoid signaling in colon cancer cells

Siddhartha Das, Leobarda Robles Martinez, Suparna Ray
Review

Phospholipid remodeling and eicosanoid signaling in colon cancer cells

Siddhartha Das et al. Indian J Biochem Biophys. 2014 Dec.

Abstract

Phospholipid remodeling and eicosanoid synthesis are central to lipid-based inflammatory reactions. Studies have revealed that membrane phospholipid remodeling by fatty acids through deacylation/reacylation reactions increases the risk of colorectal cancers (CRC) by allowing the cells to produce excess inflammatory eicosanoids, such as prostaglandins, thromboxanes and leukotrienes. Over the years, efforts have been made to understand the lipid remodeling pathways and to design anti-cancer drugs targeting the enzymes of eicosanoid biosynthesis. Here, we discuss the recent progress in phospholipid remodeling and eicosanoid biosynthesis in CRC.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Fatty acid remodeling of membrane phospholipid (compartment A). The existing fatty acids at the SN2 position of a phospholipid is hydrolyzed by PLA2, generating a lysophospholipid molecule. Lysophospholipid serves as an acceptor of a new PUFA (usually arachidonic acid) to synthesize remodeled arachidonoyl-phospholipid catalyzed by acyl-CoA transferase enzymes. In the next step, arachidonoyl-phospholipid undergoes deacylation reaction (by PLA2) releasing free arachidonic acid. Free arachidonic acid acts as a substrate of COX and LOX enzymes of eicosanoid pathway (compartment B) and synthesizes PGs, TXA2, LTs and HETE/HPETE molecules. Compartment B: (1) arachidonic acid can be utilized by cytochrome P450 enzymes to synthesize HETEs, HPETEs and epoxyeicosatrienoic acids (EETs). (2) COX-1/COX-2 enzymes converts arachidonic acid to PGH2 and then to other PGs facilitated by 12-LOX and 15-LOX as shown in step 4; (3) 5-LOX converts arachidonic acid to various LTs. (5) 15-, 12- and 8-HPETEs are synthesized from arachidonic acid by the help of 12- and 15-LOX enzymes. PLA2, phospholipase A2; PUFA, polyunsaturated fatty acid; PG, prostaglandin; TXA2, thromboxane A2, LT, leukotriene; HETE, hydroxyeicosatetraenoic acids; HPETE, hydroperoxyeicosatetraenoic acids; COX, cycooxygenase; LOX, lipooxygenase.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Barrow E, Hill J, Evans DG. Cancer risk in Lynch Syndrome. Fam Cancer. 2013;12:229–240. - PubMed
    1. Jones R, Adel-Alvarez LA, Alvarez OR, Broaddus R, Das S. Arachidonic acid and colorectal carcinogenesis. Mol Cell Biochem. 2003;253:141–149. - PubMed
    1. Siegel R, Desantis C, Jemal A. Colorectal cancer statistics. CA Cancer J Clin. 2014;64:104–117. - PubMed
    1. Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev. 2010;19:1893–1907. - PubMed
    1. Pathy S, Lambert R, Sauvaget C, Sankaranarayanan R. The incidence and survival rates of colorectal cancer in India remain low compared with rising rates in East Asia. Dis Colon Rectum. 2012;55:900–906. - PubMed

Publication types

MeSH terms

LinkOut - more resources