The fusion of autophagosomes with lysosomes was occasionally observed

percentage of proliferating cells to 46% and 29%, respectively. Data collected from 12 independent experiments revealed that treatment with WEV significantly reduced the proliferative capacity of MM cells in response to CXCL12. Moreover, although NP had no effect, the inhibitory effect of WEV+NP on the CXCL12induced proliferation of MM cells was stronger than that of WEV alone. WEV+NP Induces Apoptosis in MM Cells The inhibition of cancer cell proliferation, the cessation of cell cycle progression and the induction of apoptosis have all been targeted in chemotherapeutic strategies for the treatment of MM. Snake Venom Induces Apoptosis in Human MM Cells isolated from 12 patients. The data indicate that treatment with WEV alone and WEV+NP significantly potentiated apoptosis in MM cells. Although NP 19668186 had no significant effect on apoptosis induction in MM cells, the combination of NP with WEV significantly increased apoptosis induction compared to WEV alone. WEV and WEV+NP Modulate the Chebulinic acid web expression of Bcl-2 Family Members and Alter the Mitochondrial Membrane Potential of MM Cells and WEV+NP significantly abolished the expression of the anti-apoptotic proteins Bcl-2, Bcl-XL and Mcl-1. In contrast, a significant increase in the expression of the pro-apoptotic proteins Bak, Bax and Bim was observed after treatment with WEV and WEV+NP. Furthermore, treatment with NP alone had no effect on the expression of the Bcl-2 family proteins. Bcl-2 family proteins function upstream of irreversible cellular damage, and much of their activity occurs at the level of the mitochondrial membrane; thus, they play a pivotal role in determining if a cell lives or dies. We therefore monitored the changes in the 18690793 mitochondrial membrane potential of MM cells following treatment with WEV and WEV+NP using JC-1 dye and flow cytometry analysis. Snake Venom Induces Apoptosis in Human MM Cells brane potential. Although treatment with NP had no significant effect, the effect of WEV+NP treatment on the expression of Bcl-2 family proteins and the mitochondrial membrane potential was stronger than treatment with WEV alone. Discussion Although snake venom has been previously reported to induce apoptosis in many cancer cell lines, there is presently no information on the effect of snake venom on human MM cells and its molecular mechanism of action. In this study, we aimed to delineate the impact of WEV alone or WEV+NP and clarify the underlying effector mechanisms in primary MM cells isolated from MM patients as well as in 2 MM cell lines, U266 and RPMI 8226. Pharmacologically targeting cell cycle arrest has been effectively used as a therapeutic strategy to restrict tumor growth in vitro and in vivo. Here, we found that WEV alone or in combination with silica nanoparticles inhibited the growth of MM cells in a dose- and time-dependent manner. The effect peaked at 12 h and decreased thereafter indicating that WEV-mediated cytotoxicity effect on MM cells do not require de novo transcription. Moreover, the combination of WEV and NP enhanced the effect of WEV on these cancer cells. Furthermore, the IC50s of WEV and WEV+NP for the growth inhibition of MM cells were 25 mg/ 10 Snake Venom Induces Apoptosis in Human MM Cells ml and 10 mg/ml, respectively. Similar results were observed in our recent study that demonstrated that the growth inhibition of breast cancer cells is related to apoptosis and cell cycle arrest. Chemokines and their receptors play essential roles in the development,