Caudatin induces caspase-dependent apoptosis in human glioma cells with involvement of mitochondrial dysfunction and reactive oxygen species generation.

Caudatin as one species of C-21 steroidal from Cynanchum bungei decne displays potential anticancer activity. However, the underlying mechanisms remain elusive. In the present study, the growth suppressive effect and mechanism of caudatin on human glioma U251 and U87 cells were evaluated in vitro. The results indicated that caudatin significantly inhibited U251 and U87 cell growth in both a time- and dose-dependent manner. Flow cytometry analysis revealed that caudatin-induced cell growth inhibition was achieved by induction of cell apoptosis, as convinced by the increase of Sub-G1 peak, PARP cleavage and activation of caspase-3, caspase-7 and caspase-9. Caudatin treatment also resulted in mitochondrial dysfunction which correlated with an imbalance of Bcl-2 family members. Further investigation revealed that caudatin triggered U251 cell apoptosis by inducing reactive oxygen species (ROS) generation through disturbing the redox homeostasis. Moreover, pretreatment of caspase inhibitors apparently weakens caudatin-induced cell killing, PARP cleavage and caspase activation and eventually reverses caudatin-mediated apoptosis. Importantly, caudatin significantly inhibited U251 tumour xenografts in vivo through induction of cell apoptosis involving the inhibition of cell proliferation and angiogenesis, which further validate its value in combating human glioma in vivo. Taken together, the results described above all suggest that caudatin inhibited human glioma cell growth by induction of caspase-dependent apoptosis with involvement of mitochondrial dysfunction and ROS generation.

Alleviation of brain edema by L-arginine following experimental subarachnoid hemorrhage in a rat model.

Decreased levels of nitric oxide play a role in the development of cerebral ischemia secondary to subarachnoid hemorrhage (SAH). The protective effect of L-arginine on brain edema following SAH was investigated in this study. Rats were divided randomly into a sham-operated, a SAH+saline group and a SAH+L-arginine group. At different time points, brain water content was determined using the wet and dry weight compared method. Brain sodium content, potassium content and calcium content were detected using an atomic absorption spectral photometer. Somatosensory evoked potentials (SEP) were also detected. It was found that rat SAH models were successfully replicated. In the SAH+saline group, brain water and sodium content were significantly higher at 6 h and 24 h than those in the sham-operated group, while brain potassium content was statistically lower than that in the sham-operated group. Brain calcium content increased from 1 h to 24 h after induction of SAH. SEP latency progressively delayed. In the SAH+L-arginine group, increases in brain water content, sodium content and calcium content, as well as decreases in brain potassium content, were not as obvious as in the SAH+saline group. L-arginine partly prevented a delay in SEP latency. In conclusion, L-arginine, a substrate of nitric oxide synthesis, may relieve brain edema in rats with experimental SAH.