p21 has been postulated to be involved in growth suppression and apoptosis through a p53 dependent or independent path following pressure, and cell cycle arrest may be caused by induction of p21. The finding that genetic and pharmacologic interruption HCV NS3-4A protease inhibitor of the JNK pathway attenuated GSEmediated lethality suggests that anxiety pathways play a crucial practical position in GSE induced apoptosis. The inhibition of JNK by its specific inhibitor, SP600125, abolished the activation of caspase 3, 8, 9, PARP cleavage, and apoptosis induced by GSE. The disturbance by JNK siRNA also efficiently restricted GSE mediated activation of caspase 3, 8, 9, PARP cleavage, and apoptosis. JNK activity is apparently primarily involved with progression of numerous cell types induced by a variety of different apoptotic stimuli. JNK activity is controlled by various different systems in cells underneath the different experimental conditions. A recent study indicates that one of the mechanisms through which JNK activation depends on activation of the caspase cascade. It’s mentioned that TNF and Metastatic carcinoma anti Fas antibody induced extended JNK and ERK, and ROS accumulation were completely inhibited with a caspase inhibitor, suggesting that these events might be downstream of the caspase cascade. Meanwhile, activation of JNK 6 also works upstream of caspase activation and mitochondrial damage in toys mediated wedding of the apoptotic cascade. It’s been noted that inhibition of JNK activation by whether specific inhibitor of JNK, SP600125, or JNK siRNA abrogated 2 methoxyestradiolmediated caspase activation and apoptosis. Both stress is abrogated by blocking JNK by either dominant negative mutant or cotreatment with a specific JNK inhibitor, SP600125, induced activation of caspases, release of Smac, and induction of apoptosis. Consequently, JNK activation in stress-induced cell death might be caspase dependent or independent. In the present research, cotreatment of cells with the caspase inhibitor Z VAD FMK, which abrogated GSE induced activation of caspases and apoptosis, has failed to prevent JNK activation. Such studies Cyclopamine 4449-51-8 indicate that activation of JNK by GSE doesn’t represent a second, caspase dependent function. It was also noted that inhibition of JNK activation by the certain JNK inhibitor, SP600125, or JNK siRNA blocks activation of caspases and apoptosis. Moreover, enforced activation of JNK significantly enhanced GSE induced caspase activation and apoptosis. These data suggest that activation of JNK operates the upstream of caspase activation. That anxiety pathway plays a critical functional role in apoptosis induction by GSE. Our present study has unveiled that GSE causes strong up-regulation of Cip/p21 expression in human leukemia cells. p21 protein is an inhibitor of cyclin dependent kinase and plays an essential part in regulating CDK activity and cell cycle progression in response to a wide number of stimuli.