Jan Pokorny

High oleic acid oil suppresses lung tumorigenesis in mice through the modulation of extracellular signal-regulated kinase cascade

This study was undertaken to estimate the effect of dietary high oleic acid oil (OA) on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in mice. Diet containing 10% oil was fed to mice through experimental periods. On day 30 after NNK injection (100 mg/kg body weight, i.p.), the treatment increased the level of prostaglandin E2 (PGE2) as well as proliferating cell nuclear antigen, a marker of cell proliferation in a high linoleic acid oil (LA)-fed group but not in an OA-fed group. The NNK treatment also induced the activation of an extracellular signal-regulated kinase (Erk) cascade (Erk, Mek and Raf-1) in an LA-fed group. On the other hand, OA feeding abolished the NNK-induced activation of the Erk cascade. In conjugation with these events, OA feeding reduced lung tumor incidence and tumor multiplicity (percentage of mice with tumors) in mice compared with LA feeding at the 20th experimental week. These results suggest that OA suppresses lung tumorigenesis and that this suppression is correlated with the inhibition of PGE2 production and inactivation of the Erk cascade.

Protective effects of components in peanut skins against D-galactosamine-induced rat hepatic injury

The water extract powder (WEP) from normal oleic acid peanut skins at a dose of 200 mg/kg significantly inhibited the increases of serum bilirubin and the serum concentrations of AST, ALT, and GGT, marker enzymes for liver injury, in D-galactosamine (GalN)-induced liver injury rats. However, the WEP from high-oleic acid peanuts skins appeared to be less effective than that from normal ones at the same dose. trans-Resveratrol (0.67 mg/kg) and quercetin (0.67 mg/kg) were used for comparison. Their protective effects were as strong as that of the WEP from normal oleic acid peanut skins. These results indicated the ability of the WEP of peanut skins, especially from normal oleic acid peanut varieties, to ameliorate hepatic damage and suggested that they may contain the hepatoprotective agents, thought to be mainly polyphenolic compounds. Total polyphenolic content was higher in the WEP from normal oleic acid peanut skins, while the DPPH radical scavenging activity was higher in the WEP from high oleic acid peanut skins. Compared to high oleic acid peanut skins, normal oleic acid ones had a two-fold higher content of resveratrol, whereas no great differences were observed in the quercetin content analysed by reversed phase HPLC with UV detection.

Prostaglandin E 2 -dependent activation of Src-Stat3 signal pathway in human lung adenocarcinoma cells

Accumulating evidence suggests that overproduction of prostaglandin (PG) E2 attributable to induction of cyclooxygenase-2 plays an important role in the development of lung adenocarcinoma. Recently, we have reported that a PGE2 receptor, EP3 is involved in appearance of malignant phenotype of a lung adenocarcinoma cell (A549 cell). In line with our previous study, here we investigated if Src signaling could be involved in PGE2-stimulated growth of A549 cells via EP3. PGE2-dependent cell growth in A549 cell positively related to the activation of Src. A specific antagonist against EP3 abrogated the cell growth and Src activation in the cells stimulated with PGE2. Also, the inhibition of Src activity suppressed its downstream signaling related to cell growth as well as the cell growth in the cells treated with PGE2. These results indicate that PGE2-dependent activation of Src signaling via EP3 plays an important role in growth of A549 cells.