Parthenolide reduces gene transcription of prosurvival mediators in U937 cells

In acute myeloid leukemia (AML) the functional abnormalities of osteopontin (OPN), NF-kB, PI3K/AKT/mTOR/PTEN pathway or β-catenin have been considered. Aim: To analyze the response of U937 cells to parthenolide (PTL) through the involvement of expression of OPN protein, RelB, AKT1, mTOR, PTEN and β-catenin genes. Materials and Methods: The U937 cells were treated with PTL at concentrations of 4 μM (IC25) or 6 μM (IC50) and with OPN siRNA for MTT assay and colony forming assay. Western blot analysis using antibodies against OPN was performed with lysates of PTL-treated cells. Quantitative real-time polymerase chain reaction was performed using primers for OPN siRNA, RelB, AKT1, mTOR, PTEN and β-catenin. Results: PTL reduces OPN protein level and down-regulates RelB mRNA in U937 cell line. Suppression of OPN with siRNA increases the cytotoxic effects of PTL. Also, mRNA expression of AKT1, mTOR, PTEN, and β-catenin decreases with PTL or OPN siRNA. Conclusion: Sensitivity of U937 cells to PTL can be associated with the reduction in expression of prosurvival mediators

Study Of The Correlation Between Plama Total Antioxidant Power And Two Immune System Functions (Lymphocyte Proliferation Response And Neutrophils Directed)

Body is exposed to oxidants and free radicals since birth. These compounds are highly reactive and react with different biomolecules. However living organisms possess an antioxidant system to face these compounds. Reactive oxygen species (ROS) in immune system cells, like other cells, are produced both as a part of the normal cell metabolism and during specific activities such as phagocytosis. By prevention of oxidative damages to different parts of immune cells, antioxidants provide the conditions for optimal immune system function."nMethods and Materials: This study had been carried out in Immunology section, Central laboratory of Iran blood transfusion organization and Immunology department of Medical sciences university of Tehran during March 1999 - October 1999. Correlation method was used in this study in which the correlation between plasma total antioxidant power and two main immune cells functions including lymphocytes proliferation response (LTT test by ELISA method) and neutrophils directed movement (chemotaxis test) were investigated. Sample population in this study were 60 healthy males and females aged 21-60. On each blood sample, plasma total antioxidant power (FRAP method), LTT, and chemotaxis tests were carried out. Then statistical spearman correlation between these variables were obtained."nResults: Our results reveal that there are significant correlations (P< 0.0001) between plasma total antioxidant power and the cited variables."nConclusion: It seems what is important in the functions of the immune system, is the fair balance between oxidants and antioxidants level in the body; thus we should be able to use this parameter to evaluate the functions of immune system in health and/ or disease situation

PARTHENOLIDE REDUCES GENE TRANSCRIPTION OF PROSURVIVAL MEDIATORS IN U937 CELLS

In acute myeloid leukemia (AML) the functional abnormalities of osteopontin (OPN), NF-kB, PI3K/AKT/mTOR/PTEN pathway or β-catenin have been considered. Aim: To analyze the response of U937 cells to parthenolide (PTL) through the involvement of expression of OPN protein, RelB, AKT1, mTOR, PTEN and β-catenin genes. Materials and Methods: The U937 cells were treated with PTL at concentrations of 4 μM (IC25) or 6 μM (IC50) and with OPN siRNA for MTT assay and colony forming assay. Western blot analysis using antibodies against OPN was performed with lysates of PTL-treated cells. Quantitative real-time polymerase chain reaction was performed using primers for OPN siRNA, RelB, AKT1, mTOR, PTEN and β-catenin. Results: PTL reduces OPN protein level and down-regulates RelB mRNA in U937 cell line. Suppression of OPN with siRNA increases the cytotoxic effects of PTL. Also, mRNA expression of AKT1, mTOR, PTEN, and β-catenin decreases with PTL or OPN siRNA. Conclusion: Sensitivity of U937 cells to PTL can be associated with the reduction in expression of prosurvival mediators