Colorectal cancer is a common cause of morbidity and mortality in the United States. Most colorectal cancers arise from preexisting adenomatous or serrated polyps. The incidence and mortality of colorectal cancer can be reduced with screening of average-risk adults 50 to 75 years of age. Randomized controlled trials show evidence of reduced colorectal cancer-specific mortality with guaiac-based fecal occult blood tests and flexible sigmoidoscopy. There are no randomized controlled trials on the effectiveness of colonoscopy to reduce colorectal cancer-specific mortality; however, several randomized controlled trials comparing colonoscopy with other strategies are in progress. The best available evidence supporting colonoscopy is from prospective cohort studies that demonstrate decreased incidence of colorectal cancer and colorectal cancer-related mortality in individuals undergoing colonoscopy. Other screening options include fecal immunochemical testing, computed tomographic colonography, and multitargeted stool DNA testing combined with fecal immunochemical testing. There is good evidence that aspirin, nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitors, and hormone therapy decrease the risk of colorectal cancer and adenomatous polyps, but potential harms limit their usefulness. There is good evidence that calcium supplementation, moderate dairy consumption, reduced red meat consumption, increased physical activity, decreased body mass index, and statin use decrease the risk of colorectal cancer and adenomatous polyps. Although increased alcohol intake and tobacco use are associated with an increased risk of colorectal cancer, there is no direct evidence that reducing alcohol consumption or smoking cessation decreases the risk.

Inflammation plays a crucial role in the development of many complex diseases and disorders including autoimmune diseases, metabolic syndrome, neurodegenerative diseases, and cardiovascular pathologies. Prostaglandins play a regulatory role in inflammation. Cyclooxygenases are the main mediators of inflammation by catalyzing the initial step of arachidonic acid metabolism and prostaglandin synthesis. The differential expression of the constitutive isoform COX-1 and the inducible isoform COX-2, and the finding that COX-1 is the major form expressed in the gastro-intestinal tract, lead to the search for COX-2-selective inhibitors as anti-inflammatory agents that might diminish the gastrointestinal side effects of traditional non-steroidal anti-inflamatory drugs (NSAIDs). COX-2 isoform is expressed predominantly in inflammatory cells and decidedly upregulated in chronic and acute inflammations, becoming a critical target for many pharmacological inhibitors. COX-2 selective inhibitors happen to show equivalent efficacy with that of conventional NSAIDs, but they have reduced gastrointestinal side effects. This review would elucidate the most recent findings on selective COX-2 inhibition and their relevance to human pathology, concretely in inflammatory pathologies characterized by a prolonged pro-inflammatory status, including autoimmune diseases, metabolic syndrome, obesity, atherosclerosis, neurodegenerative diseases, chronic obstructive pulmonary disease, arthritis, chronic inflammatory bowel disease and cardiovascular pathologies.

A novel series of methylsulfonyl phenyl derivatives has been designed and synthesized to evaluate their COX-2 inhibitory activity along with anti-convulsant potential. In-vitro evaluation revealed that two compounds MTL-1 and MTL-2 appeared as most potent and selective COX-2 inhibitors in the entire series. Anti-convulsant activity of both potent COX-2 inhibitors was assessed in sc-PTZ induced seizure test and MTL-1 excellently protected animals against PTZ induced seizure at the dose of 30 mg/kg. MTL-1 also indicates long duration of action in time course study and displayed significant seizure protection up to 6 h of drug administration. Further, the anti-epileptogenic effect of MTL-1 has been examined in PTZ induced chronic model of epilepsy. The results indicated that MTL-1 had a significant anti-epileptogenic effect in PTZ kindled rats as compared to Etoricoxib (ETX) and PTZ alone treated group. Additionally, MTL-1 successfully improved cognition deficit in PTZ kindled rats, which was confirmed by social recognition, novel object recognition and light-dark chamber tests. Moreover, molecular docking and molecular simulation (MD simulation) studies were also performed to elucidate the interaction of MTL-1 with the active site of COX-2 and results showed that MTL-1 suitably binds within active site of COX-2. To investigate the safety profile of MTL-1, a sub-acute toxicity study was also performed and MTL-1 emerged as a new non-toxic chemical entity. Thus, the present investigation discovered a potent and safe COX-2 inhibitor, which is endowed with an effective anti-epileptic action.

Aspirin has cyclooxygenase-2 (COX2)-mediated anti-inflammatory and anti-coagulant properties that may confer a positive effect in preventing and limiting the progression of prostate cancer. Prostate cancer has been shown to have poor treatment outcomes due to therapeutic resistance; therefore, COX2 inhibition caused by aspirin could represent an opportunity to augment current therapies. This is particularly of interest to patients undergoing radiation therapy (RT) where inflammation is a common side-effect. This review discusses the evidence for the potential role of aspirin in the management of patients with prostate cancer undergoing RT.

Therapeutic agents aimed at inhibiting a single molecular target have not been successful in cancer therapy, but rather they impart resistance. However, multi-target inhibitors have shown promising results in circumventing the development of resistance and inducing apoptosis in cancer cells/tissues. In this study, we encapsulated doxorubicin and celecoxib in a single liposome at a ratio of 1:10. These dual drug-encapsulated liposomes showed excellent anticancer activity compared to individually encapsulated liposomes. The expression of key proteins such as AKT and COX-2 was suppressed, which suggests that doxorubicin and celecoxib synergistically inhibit multiple key signaling pathways.

Colorectal cancer (CRC) is an important cause of cancer-related deaths worldwide. Early diagnosis and treatment of CRCs are of importance for improving the survival. In the present study, we studied the effects of nonsteroidal anti-inflammatory drugs (NSAIDs)-induced chemopreventive effects on tumor development incidence and angiogenesis in experimental CRC rats. 1,2-Dimethylhydrazine dihydrochloride (DMH) was used as cancer-inducing agent and two NSAIDs (celecoxib and diclofenac) were given orally as chemopreventive agents. Histopathological and immuno histochemical evaluations were performed in colorectal tissue samples, whereas angiogenesis parameters were studied in blood samples. Histopathological examination showed that adenocarcinoma (62.5%), dysplastic changes (31.25%) and inflammattory changes (6.25%) were detected in DMH group, whereas no pathological change was observed in control rats. In treatment groups, there was marked decrease in adenocarcinoma rate (30% and 10%, respectively). A significant increase was detected in MMP-2, MMP-9 levels and MMP-2/TIMP-2 ratio in DMH group as compared with controls and treatment groups. In immunohistochemical evaluations, there was an increase in intensity and extent of staining of MMP-2 and MMP-9 in DMH group as compared to controls and treatment groups. The decrease in celecoxib group was more prominent. Overall, it was concluded that NSAIDs, particularly cyclooxygenase-2 (COX-2) inhibitors, might have a protective effect on CRC development and slow down progression of tumor in a DMH-induced experimental cancer model. One of the possible mechanisms in the chemoprevention of colon cancer seems to be inhibition of angiogenesis by diclofenac and celecoxib.

Two new sesquiterpene lactones, artelavanolides A (1) and B (2), and four known sesquiterpene lactones (3 - 6) were isolated from the leaves of Artemisia lavandulaefolia. Their structures were elucidated based on the analysis of spectroscopic data (1D, 2D-NMR and HR-ESI-MS). The absolute configuration of 1 was determined by the analysis of single-crystal X-ray diffraction data. Artelavanolide A (1) is a rare sesquiterpene lactone possessing an unusual skeleton with the linkage of Me(14)-C(1) that is probably formed through a rearrangement of the guaiane-type sesquiterpenoids. Artelavanolide B (2) is a new highly unsaturated guaianolide. Compounds 1 - 6 were tested for activities on the inhibition of COX-2 enzyme in vitro. All of compounds exhibited inhibitory activity against COX-2 with IC50 values ranging from 43.29 to 287.07 μm compared with the positive control, celecoxib (IC50 = 18.10 μm). Among them, 3 showed the best COX-2 inhibitory activity with an IC50 value of 43.29 μm.

Finding a new type of cholinesterase inhibitor that would overcome the brain availability and pharmacokinetic parameters or hepatotoxic liability has been a focus of investigations dealing with the treatment of Alzheimer's disease. Isothiocyanates have not been previously investigated as potential cholinesterase inhibitors. These compounds can be naturally produced from their glucosinolate precursors, secondary metabolites widely distributed in our daily Brassica vegetables. Among 11 tested compounds, phenyl isothiocyanate and its derivatives showed the most promising inhibitory activity. 2-Methoxyphenyl ITC showed best inhibition on acetylcholinesterase with IC50 of 0.57 mM, while 3-methoxyphenyl ITC showed the best inhibition on butyrylcholinesterase having 49.2% at 1.14 mM. Assessment of the antioxidant efficacy using different methods led to a similar conclusion. The anti-inflammatory activity was also tested using human COX-2 enzyme, ranking phenyl isothiocyanate, and 3-methoxyphenyl isothiocyanate as most active, with ∼99% inhibition at 50 μM.