dinoprost and Multiple-Myeloma

Multiple myeloma (MM) is a plasma cell malignancy comprising 15% of hematological malignancies. Many studies have assessed the relationship between free radicals and tumor progression or cancer risk. We aimed to evaluate the antioxidant activity of paraoxonase 1 (PON1), arylesterase (ARE), and 8-isoprostane in patients with stage I MM.. Spectrophotometric assays of serum PON1 and ARE activities in addition to serum 8-isoprostane level were performed in 34 patients newly diagnosed with stage I MM as compared to 35 age- and sex-matched individuals who comprised the healthy control group.. A significant reduction was found in the activities of PON1 and ARE (for both, P < 0.001) in the patient group. The ratio of PON1/high-density lipoprotein was significantly lower in the MM patient group than in the control group (P < 0.001), while 8-isoprostane levels compared with the control group were significantly higher (P < 0.001), observations that may indicate an increase in oxidative stress in stage I MM patients.. A decrease in PON1 activity and increase in 8-isoprostane serum activities in patients may indicate the importance of lipid peroxidation in MM disease. Oxidative stress and especially lipid peroxidation could reduce the antioxidant activity of PON1 and ARE in MM patients and could be considered as factors in the pathogenesis of MM disease.

Topics: Aged; Aryldialkylphosphatase; Case-Control Studies; Dinoprost; Female; Humans; Lipoproteins, HDL; Male; Middle Aged; Multiple Myeloma; Oxidative Stress

Considering possible tumorigenic activity of cyclooxygenase (COX) isozymes in myeloma, we examined expression levels of COX-1 and -2 in seven human myeloma cell lines (ARH-77, IM-9, RPMI-8226, HPC, HS-Sultan, TSPC-1, and U-266). As analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR), all the cell lines constitutively expressed COX-1, while COX-2 levels markedly varied among different cell lines. Induction of COX-2 by phorbol ester was observed in RPMI-8226 and HPC cells. In contrast, COX-2 was constitutively expressed in ARH-77 and IM-9 cells. Moreover, the high expression level of COX-2 protein in ARH-77 cells was verified by Western blotting. Intact cells of ARH-77 converted 14C-labeled arachidonic acid to prostaglandin E2, F2alpha, and D2, and this activity was dose-dependently inhibited by selective COX-2 inhibitors (SC-58125 and NS-398), a non-selective COX inhibitor (indomethacin), and relatively high concentrations of a selective COX-1 inhibitor (SC-560). These COX inhibitors also suppressed the proliferation of ARH-77 cells, but significant suppression was seen only at 100 microM, a much higher concentration than those sufficient for the COX inhibition. Moreover, proliferation of the myeloma cells lacking COX-2 was also suppressed by 100 microM of SC-58125. These results suggested that the anti-proliferative effect of the COX inhibitors is independent of the inhibition of COX-2.

Topics: Arachidonic Acid; Blotting, Western; Cell Proliferation; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; Humans; Multiple Myeloma; Phorbol Esters; Prostaglandin D2; Pyrazoles; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured