ABSTRACT
BACKGROUND: Human prostate cancer (hPCa) is the most commonly diagnosed cancer in elderly men and is the second leading cause of male cancer death. Data from epidemiological, eco-environmental, nutritional prevention and clinical trials suggest that selenium Se(IV) can prevent prostate cancer. Selol, a new organic semisynthetic derivative of Se(IV), is a mixture of selenitetriglycerides. This mixture is non-toxic and non-mutagenic, and after po treatment - 56-times less toxic (in mice) than sodium selenite. It exhibits strong anti-cancer activity in vitro in many cancer cell lines and can overcome the cell resistance to doxorubicin. Selol seems a promising compound for prostate cancer therapy. MATERIALS AND METHODS: The aim of the present study is the evaluation of Selol's influence on intracellular redox state (Eh) of prostatic tumors and the liver in androgen-dependent hPCa-bearing mice, and extracellular redox state in serum of these mice. RESULTS AND CONCLUSIONS: The anticancer activity of Selol involves perturbation of the redox regulation in the androgen dependent hPCa (LNCaP) cells, but not in healthy cells. After Selol treatment, intracellular Eh has increased in tumors from -223 mV to -175 mV, while in serum it has decreased (-82 mV vs -113 mV). It shows significant changes Eh in the extra- and intracellular environment. The difference decreases from 141 mV to 62 mV. The changes suggest that a tumor cell was probably directed toward apoptosis. This is exemplified in a significant decrease in cancer tumor mass by approx. 17% after the three weeks of Selol administration.
Subject(s)
Antineoplastic Agents/pharmacology , Selenium Compounds/pharmacology , Aged , Animals , Antineoplastic Agents/pharmacokinetics , Cysteine/metabolism , Cystine/metabolism , Extracellular Space/drug effects , Extracellular Space/metabolism , Humans , Liver/drug effects , Liver/metabolism , Male , Mice , Mice, Inbred NOD , Mice, SCID , Oxidation-Reduction , Oxidative Stress/drug effects , Prostatic Neoplasms/drug therapy , Selenium/analysis , Selenium/pharmacokinetics , Selenium Compounds/pharmacokinetics , Sulfhydryl Compounds/analysis , Tissue Distribution , Triglycerides/pharmacologyABSTRACT
The aim of the present work was to establish conditions for paraoxonase 3 (PON3) activity determination in human blood serum with simvastatin (SV) as a substrate. The activity of PON3 is considered as a good early predictor of susceptibility to premature atherosclerosis as well as of statin therapy effectiveness. The method used quantifies the SV and beta,delta-dihydroxyacid simvastatin (SVA) liberated from SV after incubation with blood serum, followed by deproteinization of the reaction mixture. Separation of SV and SVA was performed on an LC(18) column by isocratic elution with acetonitrile-K-phosphate buffer of pH 4.5 (v/v, 70:30) as a mobile phase at flow rate of 1.5 ml min(-1). Detection based on ultraviolet absorption at a wavelength of 239 nm was reliable for the simultaneous assay of SV and SVA. The applied method was sufficiently sensitive, precise and accurate for determination of low simvastatin lactone hydrolase (statinase) activity in blood serum of children (1.97-6.86 pmol min(-1) ml(-1)). The method is characterized by good linearity over the measurement range of 0.5-6 microg ml(-1) (1.194-14.3 nmol ml(-1)). Limits of detection (LOD) and quantitation (LOQ) for SV were 3.1 and 10.4 ng ml(-1), respectively. In case of SVA, LOD and LOQ were 4.7 and 14.44 ng ml(-) for a 20 microl sample, respectively. Precision and accuracy of PON3 statinase activity determination in human blood serum with SV as substrate were satisfactory and acceptable for bioanalytical methods.
Subject(s)
Chromatography, High Pressure Liquid/methods , Esterases/blood , Aryldialkylphosphatase , Humans , Simvastatin/blood , Time FactorsABSTRACT
The aim of the present work was to develop a new HPLC method for separation of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and lysophosphatidylcholine (LPC) from small-volume samples of blood plasma. Human plasma glycerophospholipids were separated by liquid-liquid extraction method followed by solid phase extraction (SPE) on aminopropyl columns. Reversed-phase Sephasil C8 column (10 cm x 2.1 mm, I.D. 5 microm) and micropreparative chromatograph "SMART" were used for separation of PC, PE, LPC and PI from SPE phospholipids extract. Binary-step gradient of eluent A: acetonitrile-methanol (130:5, v/v) and B (0.01% trifluoroacetic acid) provided good, fast and reproducible resolution of investigated phospholipids classes in 12 min at 30 degrees C. Eluted phospholipids were detected at wavelengths lambda=235 and 254 nm. This method made it possible to determine quantitatively: 5 microg ml(-1) PC, 1 microg ml(-1) LPC, 4 microg ml(-1) PE and 3 microg ml(-1) PI in blood plasma samples.