Colorectal Carcinoma, Cyclooxygenases, and COX Inhibitors

Ganduri, Vinutna; Rajasekaran, Kruthiga; Duraiyarasan, Shrimahitha; Adefuye, Mayowa A; Manjunatha, Nisha

doi:10.7759/cureus.28579

Cited by 6 publications

(7 citation statements)

References 66 publications

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“…Differential COX-2 expression may affect the likelihood that gastrointestinal adenocarcinomas, such as CRC, may develop (9) . Since specialised COX-2 inhibitors, such as different non-steroidal anti-inflammatory medications (NSAIDs), COX-2 is of special relevance since it has been created or is being produced and may have a role in the chemoprevention of gastrointestinal neoplasms (10) .…”

Section: Introductionmentioning

confidence: 99%

Association between COX-2 Gene Polymorphism and Susceptibility to Colon and Rectal Cancer

El-Shaarawy¹,

Salman²,

Hegazy³

et al. 2023

The Egyptian Journal of Hospital Medicine

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Background: Intestinal cancer the third most prevalent malignancy and leading cause of cancer mortality worldwide, is colorectal cancer (CRC). More than one-third of colorectal cancer cases in Egypt include people under the age of 40 who are found to have the disease at an advanced stage. Due to its function in human tumours, cyclooxygenase (COX), a crucial enzyme in the prostanoid biosynthesis pathway, has drawn a lot of interest. COX-2 regulates cell proliferation, cell transformation, tumour growth, metastasis, and invasion, and so plays an important role in the origin and development of metaplastic and dysplastic tissues, as well as the beginning and progression of cancer. Increased COX-2 expression has been linked to a variety of epithelial-based premalignant and malignant lesions in the gastrointestinal system, including the colorectal area. Objectives: To investigate the probable link between COX-2 gene polymorphism and colorectal cancer risk. Methods: This is a case-control study with 100 participants. Were selected 50 with colorectal cancer (case group) from Inpatient and Outpatient Oncology Clinic, Faculty of Medicine, Menoufia University and 50 participants without colorectal neoplasia (control group) matched in age and gender with case group. With the use of the usual literature approach, the polymorphism -765G/C COX2 gene was being identified using molecular genetic analysis. Clinical and pathological data from the patient were also examined. The findings demonstrated a link between the existence of the COX2 gene polymorphism and susceptibility to colorectal cancer in this pattern, with a significant incidence of GC and CC genotype in those with colorectal cancer. Additionally, there were variations in allele frequencies between the groups. There was a greater incidence of polymorphism in the left colon when cancer patients were divided based on the location of their tumours. Results:The comparison between the two studied groups indicated the genotype distribution of COX 2 gene polymorphisms in CRC patients that was 42%, 50%, and 8% with GG, GC, and CC respectively whereas in control group, it was 76% with GG, 22% with GC, and 2% with CC .The genotypic distribution revealed statistical difference (p=0.003). The allelic frequencies were 67% who had the wild allele G and the remaining 33% had the variant allele C in CRC group while in control group there were 87% with G and 13% with C allele. The difference was statistically significant (p=0.001). The GC genotype revealed a significant risk of CRC as compared to GG genotype. Subjects carrying the C allele had a significant risk of CRC compared to those carrying the allele G Conclusion: The COX2 gene polymorphism is linked to an increased risk of colorectal cancer, particularly rectosigmoid tumours.

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Section: Introductionmentioning

confidence: 99%

Association between COX-2 Gene Polymorphism and Susceptibility to Colon and Rectal Cancer

El-Shaarawy¹,

Salman²,

Hegazy³

et al. 2023

The Egyptian Journal of Hospital Medicine

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“…The ability of celecoxib to inhibit the COX-2 enzyme with subsequent decreased PGE2, which plays a crucial role in the generation of VEGF, may be the cause of the suppression of angiogenesis translated by decreased VEGF levels by the concurrent use of celecoxib with FOLFIRI [ 23 ]. When compared to sporadic forms, COX inhibition has shown statistically significant results in lowering the risk of familial CRC [ 4 ].…”

Section: Reviewmentioning

confidence: 99%

“…About five percent of new-onset CRC cases have a genetic component associated with carcinogenesis [ 2 , 3 ]. It affects men more than women and is more common in developed countries, such as the USA, due to lifestyle changes, including a lack of exercise and dietary habits predominantly involving meat and alcohol [ 4 ]. Fruits and dietary fiber are important components of a healthy diet and have been associated with various health benefits, including potential protective effects against CRC [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Long-Term Usage of Cyclo-Oxygenase-2 Inhibitors on Colorectal Cancer in Genetically Predisposed Individuals and Their Overall Effect on Prognosis: A Systematic Review

Narayana,

Mushtaq,

Shaman Ameen

et al. 2023

Cureus

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Colorectal cancer (CRC) is a major global health concern, accounting for significant cancer-related morbidity and mortality worldwide. Despite advancements in early detection and treatment modalities, the prevention of CRC remains a critical goal. Cyclo-oxygenase-2 (COX-2) is an inducible enzyme involved in the production of pro-inflammatory prostaglandins, which play a crucial role in various cellular processes, including inflammation, cell proliferation, apoptosis, and angiogenesis. Elevated COX-2 expression has been consistently observed in colorectal tumors, indicating their role in the pathogenesis of cancer. COX-2 inhibitors, such as celecoxib and rofecoxib, have been studied as potentially effective treatment modalities due to their ability to decrease prostaglandin levels, which are generally higher in cancer patients. Aberrant prostaglandin production is linked to the adenoma-carcinoma sequence, during which adenomas turn dysplastic and accumulate enough damage to become malignant. COX-2 inhibitors have also been shown to modulate various signaling pathways involved in CRC development, such as wingless-related integration site/β-catenin (Wnt/β-catenin), mitogen-activated protein kinase (MAPK), and phosphoinositide-3-kinaseprotein kinase B/Akt (PI3K/Akt) pathways. This systematic review aimed to evaluate the protective effects of long-term usage of COX-2 inhibitors on CRC in genetically predisposed individuals and their overall effect on the prognosis of the disease. The researchers conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and collected data from several databases, including PubMed, PubMed Central, Cochrane Library, and Web of Science. The search strategy combined keywords related to CRC, COX-2 inhibitors, protective effects, and prognosis. They identified 1189 articles and shortlisted 26 full-text articles that met the eligibility criteria. Quality assessment tools, such as the Assessment of Multiple Systematic Review (AMSTAR) for systematic reviews, the Cochrane bias assessment tool for randomized control trials, the scale for the assessment of narrative review articles (SANRA) checklist for narrative reviews, and the Joanna Briggs Institute (JBI) tool for crosssectional studies and case reports, are used. This review's conclusions will assist in determining the effectiveness of COX-2 inhibitors to prevent CRC. This review may also contribute to developing guidelines for clinicians to manage genetically predisposed individuals with CRC. Furthermore, the results of this review will shed light on the potential of COX-2 inhibitors as a preventive measure against CRC in genetically predisposed individuals.

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“…For decades, epidemiological studies have shown Sulindac, Aspirin, and Celecoxib to have a preventive action against CRC [7,8]. Sulindac and Celecoxib are beneficial in preventing the development of colorectal cancer in persons with the Adenomatous Polyposis Coli (APC) gene mutation [9]. Patients with the APC gene mutation present with adenomas in the colon, which progress into colon cancer if resection is not done [10].…”

Section: Introductionmentioning

confidence: 99%

“…Tumor cells can also produce excess PGE2, which acts in a paracrine/autocrine mechanism to promote angiogenesis through increased production of VEGF [14]. However, some reports have indicated that the effects of the drugs on CRC are more dependent on COX-independent pathways than COX-dependent pathways [9]. The claim is supported by a report that high levels of prostaglandin in-vitro and in-vivo inhibit cancer growth.…”

Section: Introductionmentioning

confidence: 99%

Identification of Potential Drugs for Colorectal Cancer Chemoprevention through Computational Analysis

Kioko¹,

Kagia²

2023

austinjpharmacolther

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Introduction: Colorectal cancer is one of the common causes of hospitalizations, readmission, and poor quality of life due to disability, pain, and death. Most drugs identified to provide chemoprevention in colorectal cancer, such as NSAIDs, have a high level of toxicity. There is need to find novel drugs targeting colorectal cancer with favorable clinical profiles. Objective: The study aimed to identify possible colorectal cancer prevention drugs by comparing the docking scores (representing potential biologic activity) of Aspirin, Sulindac, and Celecoxib with their structurally similar analogs. Materials and Methods: Ligand-based virtual screening and structure-based virtual screening were done for aspirin, sulindac and celecoxib to identify potential drug-like compounds. Compounds that passed the screening, pharmacokinetic profiling, and toxicity testing were considered possible drugs for colorectal cancer chemoprevention. Results: The study identified 7 drug-like compounds from the ZINC database. ZINC02570895, with a better docking score than celecoxib coupled with favorable toxicity and metabolic profiles, was the most appropriate drug candidate for the inhibition of PDK-1. ZINC22309227, with a better docking score and favorable pharmacokinetic profile than sulindac was the most appropriate compound for further development into a MAP Kinase inhibitor. ZINC39406706, ZINC26469982, ZINC01847506, ZINC3382343, and ZINC01682308 had favorable toxicity profiles compared to aspirin and were most suitable for development of cyclooxygenase inhibitors in colorectal cancer prevention. Conclusion: In-vivo and in-vitro tests are needed to ascertain the biological activity, synthesizability and clinical use of the compounds.

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Colorectal Carcinoma, Cyclooxygenases, and COX Inhibitors

Cited by 6 publications

References 66 publications

Association between COX-2 Gene Polymorphism and Susceptibility to Colon and Rectal Cancer

Association between COX-2 Gene Polymorphism and Susceptibility to Colon and Rectal Cancer

Protective Effects of Long-Term Usage of Cyclo-Oxygenase-2 Inhibitors on Colorectal Cancer in Genetically Predisposed Individuals and Their Overall Effect on Prognosis: A Systematic Review

Identification of Potential Drugs for Colorectal Cancer Chemoprevention through Computational Analysis

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