| BackgroundIntracranial benign glioma is growing in certain parts of the intracranial(mostly out of the neuronal tissue),with normal cell differentiation,slow growth,more able to cure the tumor.On the contrary,intracranial malignant glioma is mostly growing in the neuronal tissue,with innormal cell differentiation,rapid growth,difficult to cure.Approximately 17,000 primary brain tumors are diagnosed every year in the US,and of those,about 60%are gliomas.Treatment for brain gliomas depends on the location,the cell type and the grade of malignancy.Often,treatment is a combined approach,using surgery,radiation therapy,and chemotherapy.The radiation therapy is in the form of external beam radiation or the stereotactic approach using radiosurgery.Spinal cord tumors can be treated by surgery and radiation.The efficacy of chemotherapy in the treatment of high grade glial neoplasms has been generally disappointing.Over the last 10 years,only two chemotherapeutic agents,carmustine(1,3-bis(2-chloroethyl)-1-nitrosourea,BCNU implant)and temozolomide(TMZ),an imidazotetrazine derivative of dacarbazine,have received regulatory approval for treating malignant gliomas.High doses of BCNU are visceral toxic and cause extensive myelosuppression.Clearly,new therapies are required,though the basis for their development still lies in building on the technical strengths of current ones.Phytochemicals,or phytonutrients,are naturally occurring chemical compounds in plants that are known to be beneficial to human health,and as such,the examination of potential botanical therapies has become a new frontier for research into cancer treatmentIn this study we focused on effect of Xanthones from the fruit hull of Garcinia mangostana on Human Malignant Glioma cell and Pheochromocytoma cell,and investigated the specificity effect of Xanthones on different cells.Garcinia mangostana,a tropical fruit,also named as Shan Zhu,mountain bamboo,pour spill,Phoenix fruit,is native to the Malay Archipelago and the Sunda Islands and the Moluccas.In Southeast Asia,mangosteen fruit shell is a traditional folk medicine which is in the treatment of diarrhea,sprains,typhoid,ulcers,skin infections,anti-inflammatory and sterilization.The chemical composition and pharmacological activity of the mangosteen fruit shell have hardly reported in domestic.But there were much more articles which explored anti-malaria parasite,anti-oxidation,anti-tumor,protect the brain,cardiovascular and other biological activity of mangosteen pericarps in the foreign publications.?-Mangostin and ?-Mangostin were two kinds of Xanthones which were abundant in the mangosteen pericarps.?-Mangostin was reported to inhibit cell proliferation of PC 12 cell significationly in dose-dependent manner,and ?-Mangostin inhibited cell proliferation of U87 cell significationly in dose-dependent manner.a-Mangostin activated caspase-3,-8,-9 expression,decreased Bcl-2 and increased Bax.?-Mangostin decreased cyclin D1,increased P27.These changes promoted mitochondrial dysfunction,leading to the release of cytochrome c from the mitochondria to the cytoplasm and the induction of apoptosis.?-mangostin inhibited histamine-induced contractions in a concentration-dependent manner in the presence or absence of cimetidine,a histamine H2receptor antagonist,this suggest that a-mangostin is a novel competitive histamine Hireceptor antagonist in smooth muscle cells.?-mangostin inhibits 5-HT2A receptor does not inhibit 1-renal prostaglandin receptors,?-mangostin is a selective and competitive inhibition of 5-HT2A receptor significantly.From the extraction experiment of Sun Li-rong,we got 17 kinds of Xanthones from mangosteen pericarps.Our main work is to investigate the effect of these xanthones on the proliferation of PC12 cell and U87 cell,and expore much more compositions which inhibit the proliferation of glioma cells,eventually push the improved treatment of intracranial malignant glioma.ObjectiveTo determine whether the xanthones from mangosteen pericarps can inhibit the proliferational activity of PC12 cell and U87 cell.Methods1 Cell culturePC 12 cell was cultured in DMEM medium contained 10%fetal bovine serum,5%horse serum,100U/ml penicillin and 100mg/ml streptomycin.U87 cell was cultured in DMEM medium contained 10%fetal bovine serum,100U/ml penicillin and 100mg/ml streptomycin.Both cells were placed in an incubator at 37? with.5%carbon dioxide.2 MTT assayCells were seeded into 96-well plates(about 3000 cells/well)and were treated with six concentration gradient:1.25?g/ml,2.5?g/ml,5?g/ml,10?g/ml,20?g/ml,40?g/ml,then the cells were incubated for 48h.subsequently,MTT was added to the culture medium tp yield a final MTT concentration of 800?g/ml,Cells were incubated with the MTT for 4h in the incubator,then collected and dissolved in DMSO.Colorimetric analysis at 570nm was measured.3 FCM assayCell apoptosis was performed by flow cytometry for the treated group and the control group.Cells were treated with 40?g/ml?-Mangostin,then incubated for 48h,collected cells and add Annexin-FITC and PI,after dark reaction for 10minutes,cells were analyzed using FCM,Results1 MTT assayOn PC12 cell,?-mangostin??-mangostin?ep??-1-2??-1-5??-2-1??-2-3??-2-X??-3-3??-1-2??-1-5??,these twelve kinds of xanthones can significantly inhibit the cell proliferation activity with dose-dependent.On U87 cell,a-mangostin??-mangostin?ep??-1-2??-1-5??-2-1??-2-3??-2-X??-3-1??-3-3??-1-2??-1-4??-1-5??-1-6?hu,these fifteen xanthones can inhibit the cell proliferation activity significantly with dose-dependent.2 FCM assayThe effect of y-mangostin on the apoptosis of PC 12 cell was studied by FCM.It showed thaty-mangostin induced the apoptosis of PC 12 cell significantly.ConclusionThrough MTT assay,we investigate the inhibition effect of twenty one xanthones on PC 12 cell and U87 cell proliferation.In this study,we have expored many kinds of xanthones which inhibit the proliferation of glioma cells,at the same time,we have identified the effective range of dosages.We believe this study will provide a basis for further investigation of their pharmacological activity and mechanism. |
PDF Full Text Request