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.
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).
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.
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.
Several clinical studies indicated that the daily use of aspirin or acetylsalicylic acid reduces the cancer risk via cyclooxygenases (Cox-1 and Cox-2) inhibition.
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.
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.
COX-2 mediated hypoxia within the TME along with its positive interactions with YAP1 and antiapoptotic mediators are all in favor of cancer cell resistance to chemotherapeutic drugs.
Indometacin, a well‑known anti‑inflammatory drug and a non‑selective inhibitor of COX‑2, has been shown to exert anticancer effects in various types of cancer, including PDAC.
Resveratrol is a stilbenoid phytoalexin which binds to a specific site on the cell surface integrin αvβ3 to trigger cancer cell death via nuclear translocation of COX-2.
The potential of COX-2 inhibitors in cancer prevention and treatment has been shown repeatedly; however, their clinical use is limited due to toxicity.
Non-steroidal anti-inflammatory drugs (NSAIDs) are a group of molecules which have been found to be active against cancer cells with chemopreventive properties by targeting cyclooxygenase (COX-1 and COX-2) and lipoxygenase (LOX), commonly upregulated (particularly COX-2) in malignant tumors.
The physiological consequences of COX-2 overexpression in the development of cancer, diabetes and neurodegenerative diseases have made this enzyme a promising therapeutic target.
To elucidate the involved mechanisms, two colon-relevant metabolites of the polyphenolic and fiber PMD components, urolithin-A (u-A) and sodium butyrate (SB), are tested alone or in combination in vitro (colon cancer cells), and ex vivo in adenoma (AD) and normal mucosa (NM) from Pirc rats. u-A 25 μm plus SB 2.5 mm (USB) causes a significant reduction in COX-2 protein expression compared to untreated controls (about -70% in cancer cell cultures, AD, and NM), and a strong increase in C-CASP-3 expression in cells (about ten times), in AD and NM (+74 and +69%).
COX-2 is induced by pro-inflammatory cytokines at the site of inflammation and enhanced COX-2-induced synthesis of prostaglandins stimulates cancer cell proliferation, promotes angiogenesis, inhibits apoptosis, and increases metastatic potential.
This effect of mal B was strongly associated with the concomitant decrease in anti-apoptotic (IAP1, IAP2 and survivin), angiogenic (growth factors) and cancer invasiveness (matrix metalloproteinase-9, COX-2) modulating proteins.