Whilst 99.3% of the core reactions were classified as housekeeping also in normal tissues, we identified reactions catalyzed by ARG2, RHAG, SLC6 and SLC16 family gene members, and PTGS1 and PTGS2 as core exclusively in cancer.
Among nonsteroidal anti-inflammatory drugs (NSAIDs), licofelone is a triple inhibitor of both cyclooxygenases (COX-1 and COX-2) and of 5-lipooxygenase (5-LOX) that has shown some encouraging results in cancer prevention models.
Rejuvenating and recent avenues for COXIBS (selective COX-2 inhibitors) explains its integrated role in identification of biochemical pain signaling as well as its pivotal key role in cancer chemotherapy.
The main current treatments against platelets are: (1) acetylsalicylic acid (aspirin) and nonsteroidal anti-inflammatory drugs, nonselective cyclo-oxygenase (COX)-1 and COX-2 inhibitors, which are associated with decreased cancer incidence and better overall survival and (2) irreversible inhibitor of P2Y12 subtype which decreases cancer incidence.
Among them, compound A33 displayed the most potency against cancer cell lines (IC<sub>50</sub> = 6.43-10.97 μM for F10, HeLa, A549 and MCF-7 cells), lower toxicity to non-cancer cells than celecoxib (A33: IC<sub>50</sub> = 194.01 μM vs.celecoxib: IC<sub>50</sub> = 97.87 μM for 293T cells), and excellent inhibitory activities on COX-2 (IC<sub>50</sub> = 0.17 μM) and 5-LOX (IC<sub>50</sub> = 0.68 μM).
A potential pathway associated with the aforementioned issue is cyclooxygenase-2 inhibition, particularly as the overexpression of this enzyme has been proven to occur in cancer tissues and is also associated with a poor prognosis in several types of human malignancies.
The results of this study indicate that the new derivatives of OAO and particularly their conjugates with ASP, downregulate the expression of COX-2 in HepG2 cells by modulating the NF-κB signaling pathway and suggest their potential application in the prevention of liver inflammation and cancer.
Cyclooxygenase-2 (COX-2), as a potential target of cancer chemoprevention, has been played pivotal roles in proliferation of tumor cells and carcinogenesis.
Hp contribution to carcinogenesis is related to oncogenic gastrin, cyclooxygenase-2, and prostaglandins; Ki-67 is also expressed and represents an index of BE-related malignancy.
The present work sheds light on the complex modulation of cyclooxygenase-2 by endogenous heme and support the idea that targeting heme metabolism could be a valuable therapeutic option against cancer.
We analyzed the frequency of dysplastic crypts and expression of metallothionein as a biomarker of the cancer risk, as well the expression of phosphorylated H2A histone family/member X (γH2AX) for DNA damage and cyclooxygenase-2 (COX-2) for inflammatory response.
Overexpressed COX-2 has become a predictive biomarker for progression of pre-malignant towards cancer in some tissues, which makes the detection of COX-2 of great value and clinical significance.
Moreover, the expression of the cell proliferation-related proteins E2F1, Ki-67, and cancer related protein cytokeratin 19 and Cox-2 increased in response to combined treatment with NDMA and ESP.
Recent studies have identified a role of cyclooxygenases, particularly inducible isoform cyclooxygenase-2 (COX-2) and its metabolite prostaglandin E2 (PGE<sub>2</sub>) in cancer cell proliferation, and its inhibition become a target for control of cancer development, particularly in the view of recognized additive or synergic action of COX-2 inhibitors with other forms of therapy.
Our results demonstrate differences in protein and lipid profiles after inhibition of mPGES-1 or COX-2 with important implications on the therapeutic potential of mPGES-1 inhibitors as adjuvant treatment in cancer.
Nonsteroidal anti-inflammatory drugs (NSAIDs) and particularly selective cyclooxygenase-2 (COX-2) inhibitors such as celecoxib (Cxb) are considered promising cancer chemopreventive for colon, breast, prostate, lung, and skin cancers.
Since metabolic and proteomic profile analysis is essential for cancer prognosis and diagnosis, our hypothesis is that the analysis of correlations between these specific parameters and COX-2 state in tumors of a high number of CRC patients could be useful for the understanding of the basis of this cancer in humans.