Effects Of Evodiamine On The Proliferation And Apoptosis Of Human Glioma Cancer Cell U251

Gliomas are the most common brain tumors affecting the central nervous system andare associated with a high mortality rate. Meanwhile, Gliomas are characterized byincreased invasion and difficult therapy. Major clinical medicines for treating gliomasmerely extend the survival time for a number of months. The prognosis of glioma patientsremains poor. Therefore, development of new agents against gliomas is important. Chineseherbal medicine has long been used for treating malignancies. Several studies have shownthat extracts from a number of herbal medicines or mixtures have anticancer potential invitro, in vivo, or both. Evodiamine, a major alkaloid isolated from Evodia rutaecarpaBentham, has various pharmacological activities, such as inhibiting tumor growth andmetastatic properties. However, the effects of evodiamine on gliomas and their detailedmolecular mechanisms are not well understood.Objective To study the effect of evodiamine on human glioma cancer cell U251andto explore the mechanism.Methods Human glioma cancer cells U251were in vitro cultured. They weredivided into the blank control group and25,50and100μg.mL-1evodiamine groups. Theproliferation rate was detected at24,48, and72h using MTT assay. Hoechst33258staining was used to visualize nuclear changes and apoptotic body formation. The earlyapoptosis rate at24h was detected by flow cytometry. The expressions of apoptosis-relatedproteins were detected at48h respectively using western blot analysis.Results Compared with the control group, the growth inhibition rate weresignificantly increased in all evodiamine groups at24,48, and72h (P <0.05). evodiaminecould inhibit U251cell proliferation, and with increase of evodiamine concentration and action time extended, the effect of inhibiting the more significant. Compared to the controlcells, cells exposed to evodiamine presented typical apoptotic morphology and formationof apoptotic bodies. The early apoptosis rate was8.65%,19.47%, and28.97%in25,50and100μg.mL-1evodiamine groups, respectively, showing statistical difference whencompared with the control group. Western blotting analysis showed that the expression ofapoptosis related proteins FAS，FADD，Caspase-8and Caspase-3were significantlyupregulated, Bcl-2was downregulated and Bax was upregulated. All the aboveexperiments were in time-and dose-dependent manners.Conclusion Evodiamine significantly inhibited the proliferation and promoted theapoptosis of glioma cancer cell U251in a dose-and time-dependent manner. Themechanism may be related to the upregulation of Fas signaling pathways anddownregulation of Bcl-2/Bax.