Proteasome inhibitor will decrease the degradation of p27Kip1 and increase its expression. Furthermore, apoptosis induced by proteasome chemical generally is accompanied by the deposition of p27Kip1. In our research, MG132 improved the transcriptional and translational level of p27Kip1 in MG 6-3 cells, which can be consistent with recent studies that overexpression of p27Kip1 protein leads to apoptosis in a variety of cancer cell lines. Deposition of p27Kip1 protein might play a vital role deubiquitinating enzyme inhibitors in apoptosis. Broadly speaking, we all know that there are two pathways in apoptosis: the cell surface death receptor pathway and the mitochondriainitiated pathway. In the cell surface receptor pathway, activation of caspase 8 following its employment to the death inducing signaling complex is the death signal that is transmitted by the critical event. In the mitochondrial started route, caspase 9 is activated first. Then it activates downstream caspases such as caspase 3, 6 and 7. Eventually, activation of caspases throughout apoptosis results in-the cleavage of important mobile substrates, including poly polymerase Metastatic carcinoma and lamins. Shinoura et al. Noted that expression of P27Kip1 superior Fas ligand or caspase 8 mediated apoptosis. Zhou et al. Shown proteasome inhibitors could minimize Fas like inhibitor protein protein levels in tumors, causing increased apoptosis signaling due to increased caspase 8 activation. In this study, we found that caspase 8 was activated in MG 63 cells treated with MG132 for 48 h. When 40 mmol/L z VAD fmk, a broad spectrum caspase inhibitor, was added, caspase 8 was not triggered. This implies that the induction of apoptosis in MG 63 cells by MG132 is caspase 8 dependent. Upregulation of Bax and down-regulation of Bcl 2 was also observed in a time dependent fashion. But activation of caspase 9 and 3 wasn’t seen even after cells were treated with 10 mmol/ L MG132 for 4-8 h. Hougardy et al. Shown that MG132 plus rhTRAIL increased caspase 8 and caspase 3 activation, with concomitant cleavage of X linked inhibitor of apoptosis in HeLa cells. Lauricella et a-l. Addressed Saos 2 cells with MG132 Tipifarnib molecular weight and discovered that MG132 caused fragmentation of procaspase 3 and generation of the active form of caspase 3 but was not able to cause fragmentation of procaspase8. Nevertheless, we found the alternative results on MG 63 cells. Saos 2 cells lack p53 and contain a form of pRb. MG 6-3 cells absence p53 gene but have practical pRb. p53 and the retinoblastoma protein are services and products of tumor suppressor genes, which are simple within the get a handle on of cell proliferation. The term degree of pRb phosphorylation is very important to MG 63 cells D-e Blasio et a-l. hypothesized a cross-talk between pRb and PARP. It’s known that non caspase proteases are able to communicate with apoptosis via the trails.