The cyclooxygenase-2 (COX-2) is a key enzyme in the conversion of arachidonic acid to prostaglandins, which promote cell proliferation, angiogenesis and metastasis, and inhibit apoptosis. Unlike COX-1, which is constitutively expressed isoform, COX-2 is an inducible isoform of cyclooxygenase and which may participate in inflammatory responses and contribute to inflammation and cancersthe development of colorectal cancer as well as other human cancers (1). COX-2 is not detectable detected in most normal tissues. However, it but is rapidly induced when stimulated by in response to mitogens, cytokines and tumor promoters, which leads to the leading to increased accumulation of prostanoids in neoplastic and inflamed tissues (2). COX-2 is highly expressed at high levels in intestinal tumors in rodents and humans (1). For example, Mmore than 80% of all colorectal tumors were shown to overexpress COX-2 (3-5). Epidemiologic studies have shown that taking aspirin or other nonsteroidal anti-inflammatory drugs on a regular basis could reduce mortality from colorectal cancer by 40-50% compared with those who not taking these drugs (1). One characteristic shared by all of these drugs is their ability to inhibit COX activity and/or expression (1).
Although COX-2 is expressed in 80-90% of human colon carcinoma specimens, not all colorectal cancer cell lines constitutively expressed COX-2. Constitutive expression of COX-2 was only detected in a relatively small number of established colorectal carcinoma cell lines (6). For example, human colon adenocarcinoma cell lines, HCT116 and SW480, have been described as COX-2 negative, since they did not express COX-2, neither at mRNA nor at protein level (7).
COX-2-derived prostaglandin E2 (PGE2) ...
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...t as well as when the conditioned medium will be collected, with multiple parameters in which not only COX-2 mRNA and protein as well as PGE2 levels will be observed, but also other relevant molecular markers or factors like those mentioned above.
Not only paradoxical observations of COX-2 expression and the functional activity in human colon cancer cell line have been documented, the role of PGE2 on inflammation seems also paradoxical. Although PGE2 is a potent mediator of inflammation (55), it was suggested that PGE2, endogenous COX products, also inhibit acute allergic inflammation (56). Thus, PGE2 may produce both pro- and anti-inflammatory effects (57). More extensive well-designed experiments are needed to help us to unveil the secret of COX-2 expression and the functional activity as well as their roles in physiological and pathophysiological conditions.
Montaner, B. and Perez-Tomas, R. 2001. Prodigiosin-induced apoptosis in human colon cancer cells. Life sciences, 68 (17), p. 2025-2036.
In this experiment, both BALB/c and C3H mice are induced with azoxymethane (AOM) and dextran sodium sulphate (DSS). The inflammation is caused by the administration of dextran sodium sulphate to the drinking water of the mice. While azoxymethane induction plays a role in the development to colon cancer. In this project, the development of colon cancer through the inflammation pathway is being researched. The process first starts with the of inflammation foci. Over time, it develops into hyperplasia due to the increasing capacity of cell proliferation.
...ozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445(7123):111-5.
“FDA Approves Cyramza for Stomach Cancer.” U.S. Food and Drug Administration. 21 Mar. 2014. Web. 29 Apr. 2014. .
NSAIDs mode of action is to reduce the production of prostaglandins. Prostaglandins are hormones which trigger pain and inflammation in the immediate damaged area. NSAIDs inhibit an enzyme, Cyclo-Oxygenase (COX), which is involved in the first stage of prostaglandin production. There are two variants of this enzyme; COX-1 is responsible for the normal every day production of prostaglandins whereas COX-2 is responsible for production of additional prostaglandins when the body is injured as a natural defensive response. Non-selective NSAIDs, such as Ibuprofen, inhibit both COX-1 and COX-2 whereas selective NSAIDs; Celecoxib and Etoricoxib, inhibit only COX-2 (Society for Endocrinology, 2013; Ogbru, 2009).
Chemotherapy is the treatment of a tumor with chemical agents to reduce mass or eradicate a tumor completely. There are certain mechanisms by which chemotherapy inhibits cancer. The first mechanism is cell death by cytotoxicity. Some chemical agents in certain amounts are toxic to cells. The cells die due to the toxic...
Li, Y., Wicha, M. S., Schwartz, S. J., & Sun, D. (2011, February 4). Implications of Cancer Stem Cell Theory for Cancer Chemoprevention by Natural Dietary Compounds. Retrieved December 12, 2013, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248810/
In the cells, obesity leads to the decrease in gut microbia, which in turn will increase the levels of deoxycholic acid (DCA). DCA is able to stimulate senescence-associated secretory phenotype (SASP) that has been shown to contribute to cancer development (6). SASP factors have been known to affect cell growth that has to do with inflammation and tumorigenesis promotion. IL-6 and PAI-14,5 have also been shows to increase liver cancer in obese mice (6). In a study done with mice, two different groups were fed different dietary foods. One group was fed a high-fat diet while the other followed a more normal lean die...
The Hallmarks of Cancer written by Doughlas Hanahan and Robert A. Weinberg proposed the underlying principles and the essential characteristics of the development of human tumors. This article distilled all the existing research to depict the fundamental characteristics of cancer. Hanahan and Weinberge proposed six hallmarks shared among all cancers mentioned in this article includes supporting proliferative signaling, evading growth suppressor, resisting cell death, enabling replicative immortality, sustaining angiogenesis, and tissue invasion and metastasis. Four emerging hallmarks are also introduced in this article, depicting the current 10 underlying principles shared by cancerous cells. Hanahan and Weinberg also provided specific examples of potential mechanisms for the hallmarks. All of the mechanisms of hallmarks of cancer must be fulfilled in the development of cancerous cells.
COX-1 and COX-2 are isomeric enzymes that contain peroxidase and cyclooxygenase activity which can produce prostaglandins through the activity of prostaglandin G/H synthases [10]. COX-1 produces prostanoids which serve cell “housekeeping” functions. COX-2 can be activated by inflammatory stimuli and produces prostanoids in inflammatory or proliferative diseases such as cancer. Nonsteroidal anti-inflammatory drugs (NSAIDs) are competitive inhibitors of COX. Thus the binding of NSAIDs can supress prostanoid formation [11].
However, they are identified in people with colon cancer. The most abundant bacteria in our gut and causing cancer are Proteobacteria, Firmicutes and Bacteroidetes. When colon tumor genes are analyzing, alterations in these genes are founded. APC and CTNNB1, P53 genes have deletions in people with colon cancer. In addition, DNA methylation at CpG islands are abnormal, and chromosomes are instable. All these DNA alterations mentioned due colon cancer are mentioned to occur in the stem cells in the base of the villus crypt. The crypt is occupied by a numerous of differentiated cells, which renew to generate epithelium after an injury. Bacteria induced DNA alteration, E. Coli downregulate DNA mismatch repair protein, so this mechanism enhance tumor formation. In the case of, Enteroccous faecalis produce aneuploidy in the epithelial cells, aneuploidy is an abnormal number of chromosomes in a cell. Overall, there are many factors undelaying colon cancer that need to be studied. However, formation of cancer in the colon can take place due to reduction of protective bacteria, changes in energy uptake and metabolic disorders. For future considerations, it is important to understand the place that take the
CK2 is present and widely distributed in human and is essential for cell survival. It does not appear to be oncogenic by itself, but it acts as a suppressor of apoptosis and elevated levels have been associated proliferation and growth in normal and cancer cells (Ahmad, Wang et al. 2005).
Colon cancer, also referred to as colorectal cancer, is a cancer of the colon or the rectum. Colon cancer is the third leading cause of death in both men and women and is the third most common malignancy in the United States (Kim). The following will discuss how colon cancer develops, signs and symptoms, causes, and clinical tests used to detect the disease. Prognosis, prevention, and treatment options will also be discussed.
To create a chronic inflammatory state, DSS, an agent with direct toxic effects on the colonic epithelium will be administered in drinking water to mice in multiple cycles. With sufficient duration, some of these mice will develop tumors. Tumor development is hastened in this model if administered in a pro-carcinogenic setting. These include mice pre-treated with genotoxic agent (azoxymethane [AOM]). The combination of DSS with AOM as a model for colitis associated cancer has gained popularity for its reproducibility, potency, low price, and ease of use. Mice injected with AOM and subsequently treated with DSS develop adequate tumors in as little as 7-10 weeks (Thaker et al, 2012). Hence, we use both AOM and DSS in our study. Then, EO will be orally-administered into the mouse model to test the production of mucin from the goblet cells in proximal colon and compared to the disease control. The production of mucin is crucial in protecting the intestinal barrier function from
Prostaglandins are formed by the enzymes COX1 or COX2. The prostaglandins produced by COX1 are generally responsible for the maintenance and protection of the gastrointestinal tract, kidneys, and other organs. The prostaglandins produced by COX2 are predominantly known to cause inflammation and pain responses. NSAIDs work by primarily inhibiting the formation of prostaglandins by the COX2 enzyme. As the formation of the prostaglandins produced by COX2 diminishes, pain and inflammation also