Cyclooxygenase-2 is induced by p38 MAPK and promotes cell survival

Abstract

The Na+ ionophore monensin affects cellular pH and, depending on its concentration, causes the survival or death of tumor cells. In the present study, we elucidated the survival pathway activated in U937 cells, a human lymphoma-derived cell line. These cells treated with monensin at a concentration of 5 µM were growth-arrested in G1, activated p38 mitogen-activated protein kinase (MAPK) and showed an increased expression of cyclooxygenase-2 (COX-2). The latter two molecular events were linked, as pharmacological inhibition of the MAPK did not allow COX-2 increased expression. Furthermore, we showed that p38 and COX-2 keep monensin-stressed U937 cells alive, as pharmacological inhibition of each enzyme caused cell death.

p38-Mitogen Activated Kinases Mediate a Developmental Regulatory Response to Amino Acid Depletion and Associated Oxidative Stress in Mouse Blastocyst Embryos

“…Consistently, we have observed the blastocyst cavities of p38-MAPK inhibited blastocysts to be visibly smaller than controls (Figures 1b–c′; highlighted by black arrowheads), irrespective of AA supplementation status. Reports relating to glioblastoma cancer models have also clearly uncovered p38-MAPK dependant mechanisms of cell survival, involving induction of the Cox2 gene (catalyzing the committed step in prostaglandin synthesis) (Parente et al, 2013) and that have been linked to AA starvation (Li et al, 2017). However, it is improbable p38-MAPK exerts a similar role in the mouse blastocyst ICM, as we were unable to detect any basal or induced, as the recognized mechanism of regulated expression (Smith et al, 2000), Cox2 derived mRNA transcripts in either the control or experimental conditions (data not provided), again irrespective of KSOM media AA supplementation status.…”

p38-mitogen activated kinases mediate a developmental regulatory response to amino acid depletion and associated oxidative stress in mouse blastocyst embryos

“…1b to c’; highlighted by black arrowheads), irrespective of AA supplementation status. Reports relating to glioblastoma cancer models have also clearly uncovered p38-MAPK dependant mechanisms of cell survival, involving induction of the Cox2 gene (catalysing the committed step in prostaglandin synthesis) (Parente et al, 2013) and that have been linked to AA starvation (Li et al, 2017). However, it is improbable p38-MAPK exerts a similar role in the mouse blastocyst ICM, as we were unable to detect any basal or induced, as the recognised mechanism of regulated expression (Smith et al, 2000), Cox2 derived mRNA transcripts in either the control or experimental conditions (as stated in Fig.…”

Unanticipated Mycobacterium tuberculosis complex culture inhibition by immune modulators, immune suppressants, a growth enhancer, and vitamins A and D: clinical implications

“…Safety concerns mainly address whether or not residual monensin could be detected in food from animals exposed to monensin, [65][66][67][68] or the effect of monensin on human cells in culture. [69][70][71][72][73] In a solitary case report, a young agricultural employee, naively conceptualizing that the 'growth enhancer' acted as an anabolic steroid, took three times the pro-rated lethal dose for cattle, developed fatal rhabdomyolysis, renal and cardiac failure. 74 Monensin is used extensively and safely in ruminants 60,75 and poultry.…”