ABSTRACT
Aim To estimate the inhibition of curcumin derivative C1209 on the proliferation of chronic myeloid leukemia (CML) cells involving the disruption Hsp90 chaperon function. Methods The fluorescence spec-trum experiment was applied to examine the affinity be-tween different C1209 concentrations and Hsp90, NH-sp90,MHsp90,CHsp90;fluorescence intensities were recorded in the range of 290~510 nm at 293 K,303 K and 310 K,respectively;a colorimetric assay for in-organic phosphate based on the formation of a phospho-molybdate complex and subsequent reaction with mala-chite green was used to examine the inhibitory effects of C1209 on the activity of Hsp90 ATPase. MTT assay and CFSE were used for K562 and K562/G01cell pro-liferation determination in vitro by C1209. Western blot was used to detect the client proteins and the mo-lecular chaperone of Hsp90 level. Results The disso-ciation constant KDvalues of C1209 was (14.733 ± 0.713) μmol·L-1. The interaction between C1209 and Hsp90 was driven mainly by electrostatic interac-tion. C1209 showed the strongest affinity with CHsp90. When the concentration of ATP was 1mmol· L-1,the inhibition of Hsp90 ATPase activity of C1209 with the IC50value was 11.4 μmol·L-1; C1209 showed inhibition of K562 and K562/G01cells in dose-dependent proliferation and the IC50value was 1.14 μmol·L-1and 0.56 μmol·L-1, respectively after 24 h incubation. C1209 affected the molecular chaper-one functions of Hsp90 and down-regulated Bcr-Abl, Akt, MEK, ERK, c-Raf, p-Akt, p-MEK and p-ERK protein levels which were client proteins of Hsp90 in K562 and K562/G01cells. Conclusions Curcumin derivative C1209 is Hsp90 inhibitor;C1209 has signif-icant inhibitory effects on proliferation of K562 and K562 / G01, which may be related to C1209 affecting the molecular chaperone functions of Hsp90 and down-regulating client proteins of Hsp90 level.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of different concentrations of Morinda Officialis How (MOH) extracts on microwave radiation-induced injury to the spermatogenic function of male rats.</p><p><b>METHODS</b>Forty SD male rats were equally divided into four groups: control, microwave injury model, aqueous extract of MOH treatment, and alcohol extract of MOH treatment. Models of microwave-induced injury were made by exposing the rats to microwave radiation from a microwave signal generator (900 MHz 1.0 W) at 218 microm/cm2, 12 h/d, for 2 weeks. The model rats of the two treatment groups were intragastrically given aqueous extract and alcohol extract of MOH, respectively, both at 20 g per kg per day for 2 weeks. Then we observed the growth, capture incubation period (CIP), capture times (CT), changes in testicular and epididymal weight and morphology, sperm concentration and malformation, and levels of serum testosterone.</p><p><b>RESULTS</b>Compared with the controls, the rats of the model group showed a slightly reduced body weight, markedly prolonged CIP and decreased CT (P < 0.05), significantly reduced sperm concentration (P < 0.05) and remarkably in- creased sperm malformation (P < 0.05), but no statistically significant differences in the testosterone level. The two treatment groups exhibited obviously decreased body weight, CIP and sperm malformation compared with the control group (P < 0.05) but markedly increased CT, sperm concentration and testosterone level as compared with the models (P < 0.05). The microwave radiation-induced testis injury was repaired perfectly in the two treatment groups, the epididymal ducts filled with sperm and cast-off cells.</p><p><b>CONCLUSION</b>Both aqueous and alcohol extracts of MOH can promote spermatogenesis and repair of reproductive injury induced by microwave radiation.</p>