The Role of Cyclooxygenase-2 in Colorectal Cancer

Shi, Juan; Sun, Hong; Yu, Fang; Li, Bo; Zhang, Yuan; Zhu, Yingting

doi:10.7150/ijms.44439

Cited by 91 publications

(74 citation statements)

References 116 publications

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“…Another enzyme, cyclooxygenase-2 (COX-2), is involved in arachidonic acid metabolism leading to the production of prostaglandin E 2 . Nonsteroidal anti-inflammatory drugs reveal anti-inflammatory and anti-tumor effects, especially via the inhibition of cyclooxygenase-2 activity [70,71]. To the best of our knowledge, there is no information about food peptides with similar activity.…”

Section: Pglmentioning

confidence: 99%

Characteristics of Biopeptides Released In Silico from Collagens Using Quantitative Parameters

Iwaniak

Minkiewicz

Pliszka

et al. 2020

Foods

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The potential of collagens to release biopeptides was evaluated using the BIOPEP-UWM-implemented quantitative criteria including the frequency of the release of fragments with a given activity by selected enzyme(s) (AE), relative frequency of release of fragments with a given activity by selected enzyme(s) (W), and the theoretical degree of hydrolysis (DHt). Cow, pig, sheep, chicken, duck, horse, salmon, rainbow trout, goat, rabbit, and turkey collagens were theoretically hydrolyzed using: stem bromelain, ficin, papain, pepsin, trypsin, chymotrypsin, pepsin+trypsin, and pepsin+trypsin+chymotrypsin. Peptides released from the collagens having comparable AE and W were estimated for their likelihood to be bioactive using PeptideRanker Score. The collagens tested were the best sources of angiotensin I-converting enzyme (ACE) and dipeptidyl peptidase IV (DPP-IV) inhibitors. AE and W values revealed that pepsin and/or trypsin were effective producers of such peptides from the majority of the collagens examined. Then, the SwissTargetPrediction program was used to estimate the possible interactions of such peptides with enzymes and proteins, whereas ADMETlab was applied to evaluate their safety and drug-likeness properties. Target prediction revealed that the collagen-derived peptides might interact with several human proteins, especially proteinases, but with relatively low probability. In turn, their bioactivity may be limited by their short half-life in the body.

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Section: Pglmentioning

confidence: 99%

Characteristics of Biopeptides Released In Silico from Collagens Using Quantitative Parameters

Iwaniak

Minkiewicz

Pliszka

et al. 2020

Foods

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“…Stimuli that induce COX-2 expression in cells can include proinflammatory cytokines (TNFα, IL-1) or growth factors [ 8 , 15 , 17 , 18 , 19 , 20 ]. Proinflammatory prostaglandins produced through the COX-2 pathway contribute to or induce pain, fever, and swelling, and are even implicated with types of cancer, allergy, asthma, arthritis, stroke, and Alzheimer’s disease [ 7 , 13 , 19 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

Antiinflammatory Medicinal Plants from the Ugandan Greater Mpigi Region Act as Potent Inhibitors in the COX-2/PGH2 Pathway

Schultz

Osuji

Wack

et al. 2021

Plants

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Our study investigates 16 medicinal plants via assessment of inhibition of proinflammatory enzymes such as cyclooxygenases (COX). The plants are used by traditional healers in the Greater Mpigi region in Uganda to treat inflammation and related disorders. We present results of diverse in vitro experiments performed with 76 different plant extracts, namely, (1) selective COX-2 and COX-1 inhibitor screening; (2) 15-LOX inhibition screening; (3) antibacterial resazurin assay against multidrug-resistant Staphylococcus aureus, Listeria innocua, Listeria monocytogenes, and Escherichia coli K12; (4) DPPH assay for antioxidant activity; and (5) determination of the total phenolic content (TPC). Results showed a high correlation between traditional use and pharmacological activity, e.g., extracts of 15 out of the 16 plant species displayed significant selective COX-2 inhibition activity in the PGH2 pathway. The most active COX-2 inhibitors (IC50 < 20 µg/mL) were nine extracts from Leucas calostachys, Solanum aculeastrum, Sesamum calycinum subsp. angustifolium, Plectranthus hadiensis, Morella kandtiana, Zanthoxylum chalybeum, and Warburgia ugandensis. There was no counteractivity between COX-2 and 15-LOX inhibition in these nine extracts. The ethyl acetate extract of Leucas calostachys showed the lowest IC50 value with 0.66 µg/mL (COX-2), as well as the most promising selectivity ratio with 0.1 (COX-2/COX-1). The TPCs and the EC50 values for DPPH radical scavenging activity showed no correlation with COX-2 inhibitory activity. This led to the assumption that the mechanisms of action are most likely not based on scavenging of reactive oxygen species and antioxidant activities. The diethyl ether extract of Harungana madagascariensis stem bark displayed the highest growth inhibition activity against S. aureus (MIC value: 13 µg/mL), L. innocua (MIC value: 40 µg/mL), and L. monocytogenes (MIC value: 150 µg/mL). This study provides further evidence for the therapeutic use of the previously identified plants used medicinally in the Greater Mpigi region.

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“…In particular, it has been demonstrated that the activation of the transcription factor Nuclear Factor-κB (NF-κB) in the tumor site results in production of pro-inflammatory cytokines like IL-6 and IL-1, which support proliferation and survival of cancer cells ( 67 ). NF-κB also regulates the expression of tumor necrosis factor (TNF) and cyclooxygenase 2 (COX-2), which are overexpressed in an inflammatory CRC microenvironment and are involved in tumor growth promotion ( 68 , 69 ). In addition to IL-6 and IL-1, other cytokines such as TGF, vascular endothelial growth factor (VEGF), C-X-C motif chemokine 3 (CXCL3), C-X-C motif chemokine 4 (CXCL4), and high mobility group box-1 (HMGB1) can be reprogrammed by tumor cells, giving rise to an immunosuppressive cytokine-dominated CRC microenvironment, which is a common mechanism for immunosurveillance escape of cancer ( 63 ).…”

Section: Discussionmentioning

confidence: 99%

Colorectal Carcinoma Affected Patients Are Significantly Poor Responders Against the Oncogenic JC Polyomavirus

et al. 2021

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BackgroundMany investigations reported the association between human tumors and JCPyV, a polyomavirus with oncogenic potential. The association has been supported by studies that found JCPyV footprints in CRC and gliomas of different types. Indeed, JCPyV footprints including its nucleic acids and Tag oncoprotein have been revealed in CRC tissues.MethodsHerein, sera from colorectal carcinoma (CRC) affected patients and healthy individuals (HS), employed as control, were analysed for immunoglobulin G (IgG) antibodies against specific JCPyV viral capsid protein 1 (VP1) antigens. The investigation was carried out employing an innovative immunological assay. Indeed, an indirect enzyme-linked immunosorbent assay (ELISA) with JCPyV VP1 mimotopes was used. JCPyV VP1 mimotopes consisted of synthetic peptides mimicking VP1 epitopes.ResultsSera from CRC affected patients, evaluated using indirect ELISAs with synthetic mimotopes, showed a significant lower prevalence of IgG antibodies against JCPyV VP1 mimotopes (26%) compared to HS (51%), p<0.005. These data were confirmed by another method, the hemagglutination inhibition (HAI) assay. Altogether these results, i.e. the prevalence of serum IgG antibodies against JCPyV VP1 mimotopes from patients with CRC is approximately 50% lower than in HS, are of interest.DiscussionOur data suggest that patients with CRC are significantly poor responders against JCPyV VP1 antigens. It is possible that CRC patients are affected by a specific immunological deregulation. This immunological dysfunction, revelled in CRC patients, may account for their predisposition to the colorectal carcinoma onset.

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The Role of Cyclooxygenase-2 in Colorectal Cancer

Cited by 91 publications

References 116 publications

Characteristics of Biopeptides Released In Silico from Collagens Using Quantitative Parameters

Characteristics of Biopeptides Released In Silico from Collagens Using Quantitative Parameters

Antiinflammatory Medicinal Plants from the Ugandan Greater Mpigi Region Act as Potent Inhibitors in the COX-2/PGH2 Pathway

Colorectal Carcinoma Affected Patients Are Significantly Poor Responders Against the Oncogenic JC Polyomavirus

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