The apoptosis-inducing effect of a-anordrin (ANO)was investigated in this study. ANO 10-50 AM inhibited the growth of both human leukemia HL-60 and K562cells by 19-52%. Electron microscopy showed that ANO-treated cell...The apoptosis-inducing effect of a-anordrin (ANO)was investigated in this study. ANO 10-50 AM inhibited the growth of both human leukemia HL-60 and K562cells by 19-52%. Electron microscopy showed that ANO-treated cells exhibited the drastic changes including cell shrinkage, chromatin condensation, nuclear fragmentation, typical of apoptosis. Gel electrophoresis of DNA extracted farm botlt HL-60 and K562 cells treated with ANO revealed characteristic 'ladder' pattern.ANO 50 μM for 48 h caused approximately 50-70%apoptosis. Cycloheximide (CHX) and actinomycin D (Act D) did not prevent ANO-induced apoptosis in K562cells, however, apoptosis of HL-60 cells in the presence of ANO was partially blocked by these two agents.Moreover, it was found that tamoxifen synergically potcntiated and cstradiol partially antagonized ANOinduccd apoptosis in HL-60 cells. Results demonstrated that ANO could induce tumor cell apoptosis, which might contribute to its anticancer action.展开更多
To clarify the possible mechanisms of α anordin and probimane on calmodulin Ca ++ Mg ++ APTase system, enzyme dynamic study was carried out by determining three dynamic parameters [the substrate concentra...To clarify the possible mechanisms of α anordin and probimane on calmodulin Ca ++ Mg ++ APTase system, enzyme dynamic study was carried out by determining three dynamic parameters [the substrate concentration(ATP) response curve, dose(inhibitors) response curve and time response curve]. Our data have shown that the inhibitory rates of α anordrin and probimane are unrelated to substrate(APT) concentrations, but related to calmodulin concentrations. The inhibition of α anordrin and probimane is very quick that is completed within 1 to 5 min and can maintain more than 1 hr in the same inhibitory rates. So it is possible that α anordrin and probimane are calmodulin competitors with calmodulin like binding whose actions can occur by affecting the reaction balance of substrate and product on target enzymes of calmodulin( Ca ++ Mg ++ ATPase).展开更多
Division of Reproductive Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200031, China *DEPT. Of Pharmacology, Shanghai Tiedao University, Medical College Shanghai 2000...Division of Reproductive Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200031, China *DEPT. Of Pharmacology, Shanghai Tiedao University, Medical College Shanghai 200070, China By using the morphology and the viability of cells index, the direct effects of anordrin on serum free primary cultures of rat luteal cells, human decidual cells and trophoblast cells were observed.Meanwhile, the effect of anordrin on the secretive function of rat luteal cells was also observed. The results indicated that (1) anordrin has damaging effects on rat luteal cells, human decidual cells and trophoblast cells. The LD 50 s were 14.34±0.9 μg/ml, 17.33±4.1 μg/ml and 34.87±4.9 μg/ml respectively. (2) With nonlethal dose (5 μg/ml), the activity of progesterone secretion of rat lutein cells which was stimulated by hCG and pregnenolone was not influenced by anordrin while the stimulating activity of forskolin was inhibited remarkably.The results suggest that luteolytic action is the main mechanism of the termination of early pregnancy by anordrin and the direct damaging effects of anordrin on decidua and cytotrophoblasts also play a role in the termination of early pregnancy.展开更多
To provide the theoretical fundation for the further clinical application of mifepristone and anordrin compound. Materials & Methods Ribonuclease protection assay was used for the detection and q...To provide the theoretical fundation for the further clinical application of mifepristone and anordrin compound. Materials & Methods Ribonuclease protection assay was used for the detection and quantitation of estrogen and progesterone receptor mRNAs in human decidua from the termination of early pregnancy.Three groups, each of which had 6～8 cases, were studied. Results Compared to the normal control group, estrogen and progesterone receptor mRNAs increased significantly (P<0.05) in the mifepristone group, whereas the changes in the group administrated mifepristone compound which contains anordrin were not obvious. Conclusions The result suggests that with the similar clinical effect, mifepristone compound has less side effect on the patients, thus being more suitable for the anti early pregnancy drug.展开更多
文摘The apoptosis-inducing effect of a-anordrin (ANO)was investigated in this study. ANO 10-50 AM inhibited the growth of both human leukemia HL-60 and K562cells by 19-52%. Electron microscopy showed that ANO-treated cells exhibited the drastic changes including cell shrinkage, chromatin condensation, nuclear fragmentation, typical of apoptosis. Gel electrophoresis of DNA extracted farm botlt HL-60 and K562 cells treated with ANO revealed characteristic 'ladder' pattern.ANO 50 μM for 48 h caused approximately 50-70%apoptosis. Cycloheximide (CHX) and actinomycin D (Act D) did not prevent ANO-induced apoptosis in K562cells, however, apoptosis of HL-60 cells in the presence of ANO was partially blocked by these two agents.Moreover, it was found that tamoxifen synergically potcntiated and cstradiol partially antagonized ANOinduccd apoptosis in HL-60 cells. Results demonstrated that ANO could induce tumor cell apoptosis, which might contribute to its anticancer action.
文摘To clarify the possible mechanisms of α anordin and probimane on calmodulin Ca ++ Mg ++ APTase system, enzyme dynamic study was carried out by determining three dynamic parameters [the substrate concentration(ATP) response curve, dose(inhibitors) response curve and time response curve]. Our data have shown that the inhibitory rates of α anordrin and probimane are unrelated to substrate(APT) concentrations, but related to calmodulin concentrations. The inhibition of α anordrin and probimane is very quick that is completed within 1 to 5 min and can maintain more than 1 hr in the same inhibitory rates. So it is possible that α anordrin and probimane are calmodulin competitors with calmodulin like binding whose actions can occur by affecting the reaction balance of substrate and product on target enzymes of calmodulin( Ca ++ Mg ++ ATPase).
文摘Division of Reproductive Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200031, China *DEPT. Of Pharmacology, Shanghai Tiedao University, Medical College Shanghai 200070, China By using the morphology and the viability of cells index, the direct effects of anordrin on serum free primary cultures of rat luteal cells, human decidual cells and trophoblast cells were observed.Meanwhile, the effect of anordrin on the secretive function of rat luteal cells was also observed. The results indicated that (1) anordrin has damaging effects on rat luteal cells, human decidual cells and trophoblast cells. The LD 50 s were 14.34±0.9 μg/ml, 17.33±4.1 μg/ml and 34.87±4.9 μg/ml respectively. (2) With nonlethal dose (5 μg/ml), the activity of progesterone secretion of rat lutein cells which was stimulated by hCG and pregnenolone was not influenced by anordrin while the stimulating activity of forskolin was inhibited remarkably.The results suggest that luteolytic action is the main mechanism of the termination of early pregnancy by anordrin and the direct damaging effects of anordrin on decidua and cytotrophoblasts also play a role in the termination of early pregnancy.
基金This work was supported by a grant from the National Laboratory of Contraceptives and Devices Research of China
文摘To provide the theoretical fundation for the further clinical application of mifepristone and anordrin compound. Materials & Methods Ribonuclease protection assay was used for the detection and quantitation of estrogen and progesterone receptor mRNAs in human decidua from the termination of early pregnancy.Three groups, each of which had 6～8 cases, were studied. Results Compared to the normal control group, estrogen and progesterone receptor mRNAs increased significantly (P<0.05) in the mifepristone group, whereas the changes in the group administrated mifepristone compound which contains anordrin were not obvious. Conclusions The result suggests that with the similar clinical effect, mifepristone compound has less side effect on the patients, thus being more suitable for the anti early pregnancy drug.
