Potential antioxidant activity of celecoxib and amtolmetin guacyl: <i>in vitro</i> studies

Kirkova, Margarita; Alexandova, A.; Kesiova, M.; Tsvetanova, Elina; Georgieva, Almira; Todorov, S

doi:10.1111/j.1474-8673.2006.00391.x

Cited by 9 publications

(7 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is some evidence in the literature suggesting that cyclooxygenase‐2 (COX‐2) inhibitors may exert a protective effect on DNA against oxidative damage (52–55). We explored, therefore, whether the COX‐2 inhibitor celecoxib might affect the level of CHP and CAA.…”

Section: Resultsmentioning

confidence: 99%

Cytometric assessment of DNA damage by exogenous and endogenous oxidants reports aging‐related processes

et al. 2007

View full text Add to dashboard Cite

The ongoing DNA damage caused by reactive oxygen species generated during oxidative metabolism is considered a key factor contributing to cell aging as well as preconditioning cells to neoplastic transformation. We postulated before that a significant fraction of constitutive histone H2AX phosphorylation (CHP) and constitutive activation of ATM (CAA) seen in untreated normal and tumor cells occurs in response to such DNA damage. In the present study, we provide further evidence in support of this postulate. The level of ATM activation and H2AX phosphorylation, detected immunocytochemically, has been monitored in WI-38, A549, and TK6 cells treated with H 2 O 2 as well as growing under conditions known or suspected to affect the level of endogenous oxidants. Thirty-to 60-min exposure of cells to 100 or 200 lM H 2 O 2 led to an increase in the level of H2AX phosphorylation and ATM activation, particularly pronounced (nearly fivefold) in S-phase cells. Cell growth for 24-48 h under hypoxic conditions (3% O 2 ) distinctly lowered the level of CHP and CAA while it had minor effect on cell cycle progression. Treatment (4 h) with 0.1 or 0.3 mM 3-bromopyruvate, an inhibitor of glycolysis and mitochondrial oxidative phosphorylation, reduced the level of CHP (up to fourfold) and also decreased the level of CAA. Growth of WI-38 cells in 2% serum concentration for 48 h led to a 25 and 30% reduction in CHP and CHA, respectively, compared with cells growing in 10% serum. The antioxidant vitamin C (2 mM) reduced CHP and CAA by 20-30% after 24 h of treatment, while the COX-2 inhibitor celecoxib (5 lM) had a minor effect on CHP and CAA, though it decreased the level of H 2 O 2 -induced H2AX phosphorylation and ATM activation. In contrast, dichloroacetate known to shift metabolism from anaerobic to oxidative glycolysis through its effect on pyruvate dehydrogenase kinase enhanced the level of CHP and CAA. Our present data and earlier observations strongly support the postulate that a large fraction of CHP and CAA occurs in response to DNA damage caused by metabolically generated oxidants. Cytometric analysis of CHP and CAA provides the means to measure the effectiveness of exogenous factors, which either through lowering aerobic metabolism or neutralizing radicals may protect DNA from such damage. ' International Society for Analytical CytologyKey terms H2AX phosphorylation; ATM activation; reactive oxygen species; hypoxia; hydrogen peroxide; 3-bromopyruvate; dichloroacetate; celecoxib; aging; caloric restriction; mitochondria IN living cells, nuclear DNA is constantly being damaged by endogenous reactive oxidants generated during aerobic respiration in mitochondria (1-6). Both, the firstand the second-generation reactive intermediates, the byproducts of oxidative phosphorylation reactions, can diffuse from mitochondria, reach the nuclear DNA, and induce its damage (7,8). It has been estimated that DNA exposure to endogenous oxidants during a single cell cycle of about 24-h duration results in~5,000 DNA single-strand lesi...

show abstract

Section: Resultsmentioning

confidence: 99%

Cytometric assessment of DNA damage by exogenous and endogenous oxidants reports aging‐related processes

et al. 2007

View full text Add to dashboard Cite

show abstract

“…For colon cancer, inhibition of tumor growth by celecoxibloaded liposomes was accompanied by activation of SOD, which was further related to an antioxidative activity [56]. Celecoxib also increased SOD activity in rat stomach and colon mucosa [57]. In cSCC, however, the situation was clearly different, as ROS production by celecoxib in cSCC cells was strong, rapid, and long-lasting.…”

Section: Discussionmentioning

confidence: 99%

High ROS Production by Celecoxib and Enhanced Sensitivity for Death Ligand-Induced Apoptosis in Cutaneous SCC Cell Lines

Zhu

May

Ulrich

et al. 2021

IJMS

View full text Add to dashboard Cite

Incidence of cutaneous squamous cell carcinoma (cSCC) and actinic keratosis has increased worldwide, and non-steroidal anti-inflammatory drugs as celecoxib are considered for treatment. We show here strong anti-proliferative effects of celecoxib in four cSCC cell lines, while apoptosis and cell viability largely remained unaffected. Impeded apoptosis was overcome in combinations with agonistic CD95 antibody or TNF-related apoptosis-inducing ligand (TRAIL), resulting in up to 60% apoptosis and almost complete loss of cell viability. Proapoptotic caspase cascades were activated, and apoptosis was suppressed by caspase inhibition. TRAIL receptor (DR5) and proapoptotic Bcl-2 proteins (Puma and Bad) were upregulated, while anti-apoptotic factors (survivin, XIAP, cFLIP, Mcl-1, and Bcl-w) were downregulated. Strongly elevated levels of reactive oxygen species (ROS) turned out as particularly characteristic for celecoxib, appearing already after 2 h. ROS production alone was not sufficient for apoptosis induction but may play a critical role in sensitizing cancer cells for apoptosis and therapy. Thus, the full therapeutic potential of celecoxib may be better used in combinations with death ligands. Furthermore, the immune response against cSCC/AK may be improved by celecoxib, and combinations with checkpoint inhibitors, recently approved for the treatment of cSCC, may be considered.

show abstract

“…Also in a two week twice-a-day (2.5 mg/kg) CEL administration study conducted using young rats, there was an increase in plasma MDA concentration; however, no GSH change in liver was detected 9 . While these results suggest that plasma MDA concentrations may be altered, other studies have shown that CEL administration at therapeutic drug doses does not alter either biomarker in rat livers 8 , 27 . MDA levels in the jejunum were also unchanged upon CEL exposure in a study conducted by Fornai and colleagues 29 .…”

Section: Discussionmentioning

confidence: 56%

“…No group in this study presented with a depletion of GSH pointing to equivalent oxidative stress. These results are supported by an in vitro experiment using rat liver which showed no significant change in GSH levels upon CEL exposure 8 . While a wide range of MDA concentrations were measured in the control rat livers, the absence of significance difference between the groups suggests no increased lipid peroxidation.…”

Section: Discussionmentioning

confidence: 60%

“…NSAIDs function through the inhibition of cyclooxygenase (primarily COX-1 and COX-2) reducing the production of prostaglandin (PG), a mediator of both pain and inflammation 3 , 5 , 6 . COX-1 is known to be primarily involved in homeostatic physiological processes and constitutively produced in numerous tissues; while the COX-2 isoform is inducible and found principally in association with inflammation 7 , 8 , 9 , 10 . The majority of NSAIDs inhibit both isoforms of COX and as such are classified as non-selective NSAIDs; however, celecoxib (CEL) is a COX-2-selective inhibitor which provides a more favorable gastric side effect profile compared to traditional non-selective NSAIDS 2 , 5 , 9 , 10 , 11 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Histopathology and oxidative stress analysis of concomitant misoprostol and celecoxib administration

2015

View full text Add to dashboard Cite

Nonsteroidal anti-inflammatory drugs (NSAIDs), non-selective or selective inhibitors of cyclooxygenase (COX-1 and -2), reduce pain and inflammation associated with arthritic diseases. Celecoxib, a COX-2-selective inhibitor providing decreased gastric injury relative to non-selective NSAIDs, is commonly prescribed. Misoprostol, a prostaglandin analog, supplements NSAID-inhibited prostaglandin levels. As concomitant celecoxib and misoprostol administration has been shown to intensify renal adverse effects, this article examined the influence of concomitant administration on hepatic histopathology, oxidative stress, and celecoxib concentration. On days 1 and 2, rat groups (n = 6) were gavaged twice daily (two groups with vehicle and two groups with 100 μg/kg misoprostol). From day 3 to day 9, one celecoxib dose (40 mg/kg) replaced a vehicle dose of one group and one group received celecoxib in addition to misoprostol. Livers were harvested on day 10. No hepatic abnormalities were observed denoting a lack of influence by either drug. Also no change in mean biomarker levels was detected. The changes in hepatic celecoxib concentration in the misoprostol-receiving group compared to control were not significant. Thus misoprostol does not influence hepatic celecoxib effects in terms of histopathology, oxidative stress, or celecoxib concentration level at the dosage and duration examined.

show abstract

Potential antioxidant activity of celecoxib and amtolmetin guacyl: in vitro studies

Cited by 9 publications

References 30 publications

Cytometric assessment of DNA damage by exogenous and endogenous oxidants reports aging‐related processes

Cytometric assessment of DNA damage by exogenous and endogenous oxidants reports aging‐related processes

High ROS Production by Celecoxib and Enhanced Sensitivity for Death Ligand-Induced Apoptosis in Cutaneous SCC Cell Lines

Histopathology and oxidative stress analysis of concomitant misoprostol and celecoxib administration

Contact Info

Product

Resources

About