Expression of Cytosolic Phospholipase A2α in Murine C12 Cells, a Variant of L929 Cells, Induces Arachidonic Acid Release in Response to Phorbol Myristate Acetate and Ca2+ Ionophores, but Not to Tumor Necrosis Factor-α

Abstract

Abstract. Tumor necrosis factor-a (TNFa)-induced cell death is regulated through the release of arachidonic acid (AA) by group IVA cytosolic phospholipase A 2 (cPLA 2 a ) in the murine fibroblast cell line L929. However, the signaling pathway by which TNFa activates cPLA 2 a remained to be solved. We examined AA release in L929 cells, in a variant of L929 (C12 cells) lacking cPLA 2 a, and in C12 cells transfected with cPLA 2 a expression vectors. In transient and stable clones of C12 cells expressing cPLA 2 a, Ca 2+ ionophore A23187 and phorbol myristate acetate (PMA) stimulated AA release within 90 min, although no response to TNFa was observed within 6 h. These results suggest that C12 cells may lack the components necessary for TNFa -induced AA release, in addition to cPLA 2 a. PMA is known to stimulate AA release via phosphorylation of Ser 505 in cPLA 2 a by activating extracellular signal-regulated kinases (ERK1 / 2). However, PMA-induced AA release from C12 cells expressing mutant cPLA 2 a S505A (mutation of Ser 505 to Ala), which is not phosphorylated by ERK1 / 2, was similar to that from L929 cells and C12 cells expressing wild-type cPLA 2 a . The role of Ser 505 phosphorylation in AA release induced by PMA is also discussed.

Anticancer Activity of Methanolic Leaf Extract of Morinda Tinctoria Roxb. Against Ehrlich Ascites Carcinoma in Mice

“…The tumor implantation includes a local inflammatory reaction, with increasing vascular permeability, which results in an intense ascetic fluid accumulation. The ascitic fluid is vital for tumor augmentation since it constitutes a direct nutritional source for cancer cells (Shimizu et al 2004). Our results show an increase in life span accompanied by a reduction in WBC count in MEMT treated mice.…”

“…Plant-derived extracts containing antioxidant principles such as flavonoids, phenolic compounds and tannins showed cytotoxicity towards cancer cells and anticancer activity in experimental animals (Marklund et al 1982;Li and Oberley, 1997 In EAC tumor-bearing animals, there was a regular and hurried increase in ascetic fluid volume. Ascitic fluid is the direct dietary source for tumor growth and it meets the nutritional requirements of tumor cells (Shimizu et al 2004). MEMT treatment decreased the volume of solid tumor and increases the life span of the tumor-bearing animals.…”

Effects of Synthetic Sphingosine-1-Phosphate Analogs on Cytosolic Phospholipase A2α–Independent Release of Arachidonic Acid and Cell Toxicity in L929 Fibrosarcoma Cells: the Structure–Activity Relationship

“…Interestingly, both the compounds significantly (P<0.05) inhibited the DMBmC11S (GS13)-induced release of AA. Treatment with 10 μM A23187 (Ca 2+ ionophore) released AA via activation of cPLA 2 α in L929 cells (18,24). Treatment with 30 μM DMAc-mC11S (GS22) and DMAm-mC11S (GS23) did not inhibit the A23187-induced release of AA in L929 cells; the release was 199 ± 24 (% of control, n = 6) on treatment with A23187 alone, 276 ± 22% (n = 3) with A23187/DMAc-mC11S, and 181 ± 8% (n = 3) with A23187/DMAm-mC11S.…”

“…The effects of the compounds were examined at pharmacological concentrations (10 and 30 μM). The concentrations of other reagents including enzyme inhibitors were the same as those in previous reports (18,24,25). The S1P analogs having a dimethylated phosphate group were dissolved in dimethyl sulfoxide, and the final concentration of dimethyl sulfoxide was under 0.5%.…”

Antitumor Activity of the Methanol Extract of Hypericum hookerianum Stem Against Ehrlich Ascites Carcinoma in Swiss Albino Mice

“…The Ehrlich ascitic tumor implantation induces per se a local inflammatory reaction, with increasing vascular permeability, which results in an intense edema formation, cellular migration, and a progressive ascitic fluid formation (23). The ascitic fluid is essential for tumor growth, since it constitutes a direct nutritional source for tumor cells (20). The packed cell volume and the number of viable EAC tumor cells in peritoneum were significantly lower in mice treated with MEHH when compared to the tumor control group.…”