Extracellular signal-regulated kinase phosphorylation due to menadione-induced arylation mediates growth inhibition of pancreas cancer cells.

BACKGROUND: Cytotoxicity of Vitamin K3 (VK3) is indicated to have the same mechanism with oxidative stress (H(2)O(2)). In the present study, we analyzed the differences and/or similarities in the cellular responses to oxidative stress and VK3 to clarify the mechanism of growth inhibition. METHODS: Cell viability was determined by a test method with 3-[4, 5-dimethyl-thiazol]-2, 5-dephenyl tetrazolium bromide (MTT). Expressions of cellular proteins were evaluated by Western blot analysis. RESULTS: The IC50 was calculated to be 47.3 +/- 4.1 microM for VK3 and 2.2 +/- 1.2 microM for H(2)O(2). By Western blot analysis, VK3 or H(2)O(2) was shown to induce rapid phosphorylation of extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinases (JNKs). H(2)O(2)-induced phosphorylation of ERK and JNK was almost complete inhibited by more than 100-muM genistein. VK3-induced JNK phosphorylation was blocked by 100-microM genistein, but ERK phosphorylation was not inhibited completely even if 400-microM genistein was used. H(2)O(2)-induced inhibition of cell proliferation was completely blocked by 400-microM genistein, but the VK3 effect was reduced 72.8 +/- 5.4% by the same concentration of genistein. H(2)O(2)-induced JNK phosphorylation and ERK phosphorylation were inhibited by staurosporine, protein kinase C (PKC) inhibitor. VK3-induced JNK phosphorylation was also blocked, but ERK phosphorylation was not affected. Staurosporine had no effect on VK3- or H(2)O(2)-induced growth inhibition. Treatment with a non-thiol antioxidant agent, catalase, completely abrogated H(2)O(2)-induced JNK and ERK phosphorylation, but a thiol antioxidant, L: -cystein, had no effect on phosphorylation of them. The VK3-induced JNK phosphorylation was inhibited by catalase, but not L: -cystein. But ERK phosphorylation was not inhibited by catalase and was abrogated completely by the thiol antioxidant. Catalase, but not L: -cystein, blocked H(2)O(2)-induced growth inhibition, and L: -cystein, but not catalase, blocked VK3-induced effects on cell proliferation completely. CONCLUSION: VK3-induced ERK phosphorylation occurs by a different mechanism from oxidative stress, and it might have an important role to induce growth inhibition.

Ileal perforation in a patient with high spinal cord injury: report of a case.

Assessing abdominal complications in patients who have previously suffered high spinal cord injury is very difficult because the resultant loss of sensory, motor, and reflux function of the abdominal wall can mask the typical signs of acute abdomen such as tenderness, muscle rigidity, and peritoneal rebound pain. We recently diagnosed a small intestinal perforation in a 77-year-old man with a C6-7 spinal cord injury sustained 14 years earlier. The patient was correctly diagnosed as having an acute abdominal condition, despite palsy of abdominal wall sensation. An emergency laparotomy was done and a 40-cm length of affected ileum, about 180 cm distal to the Treitz ligament, including a 1-cm perforation, was resected, followed by an end-to-end anastomosis. We report this case to raise awareness of the need for appropriate diagnosis and early surgical treatment of abdominal complications in spinal-cord-injured patients.