Apoptotic activity of caged xanthones from Garcinia hanburyi in cholangiocarcinoma cell lines

查看全文 作　　者：Chariya [1]Hahnvajanawong;Wongwarut [1]Boonyanugomol;Tapanawan [1]Nasomyon;Watcharin [2]Loilome;Nisana [2]Namwat;Natthinee [3]Anantachoke;Wichittra [4]Tassaneeyakul;Banchob [5]Sripa;Wises [1]Namwat;Vichai [6]Reutrakul 机构地区：[1]Department of Microbiology,Center of Excellence for Innovation in Chemistry,and Liver Fluke and Cholangiocarcinoma Research Center,Faculty of Medicine,Khon Kaen University;[2]Department of Biochemistry,Faculty of Medicine,Khon Kaen University;[3]Department of Pharmacognosy,Faculty of Pharmacy,Mahidol University;[4]Department of Pharmacology,Faculty of Medicine,Khon Kaen University;[5]Department of Pathology,Faculty of Medicine,Khon Kaen University;[6]Department of Chemistry,and Center of Excellence for Innovation in Chemistry,Faculty of Science,Mahidol University 出　　处：《World Journal of Gastroenterology》索引2010年第16卷第18期,共9页 基　　金：Supported by Grants from the Center of Excellence for Innovation in Chemistry,Commission on Higher Education,No 48-03-3-00-144;Faculty of Medicine,No 51-03-2-00-008 and Khon Kaen University,No 50-03-1-01-005,Research Funds,Khon Kaen University,Thailand 摘　　要：AIM:To investigate the growth inhibitory mechanism of four caged xanthones from Garcinia hanburyi in cholangiocarcinoma(CCA) KKU-100 and KKU-M156 cells.METHODS:Four caged xanthones,selected on the basis of their anticancer potency and chemical structure diversities(i.e.isomorellin,isomorellinol,forbesione and gambogic acid) were used in this study.Growth inhibition of these caged xanthones was determined using the sulforhodamine B assay.Induction of apoptosis was assessed by observing cell morphology,ethidium bromide and acridine orange staining and DNA fragmentation assay.Levels of apoptotic-related gene and protein expressions were determined by a real-time reverse transcriptase polymerase chain reaction and Western blotting analysis,respectively.RESULTS:The compounds were found to inhibit growth of both cell lines in a dose-dependent manner and also showed selective cytotoxicity against the cancer cells when compared with normal peripheral blood mononuclear cells.Growth suppression by these compounds was due to apoptosis,as evidenced by the cell morphological changes,chromatin condensation,nuclear fragmentation,and DNA ladder formation.At the molecular level,these compounds induced down-regulation of Bcl-2 and survivin proteins with up-regulation of Bax and apoptosisinducing factor proteins,leading to the activation of caspase-9 and-3 and DNA fragmentation.The functional group variations did not appear to affect the anticancer activity with regard to the two CCA cell lines;however,at a mechanistic level,isomorellinol exhibited the highest potency in increasing the Bax/Bcl-2 protein expression ratio(120 and 41.4 for KKU-100 and KKU-M156,respectively) and in decreasing survivin protein expression(0.01 fold as compared to control cells in both cell lines).Other activities at the molecular level indicate that functional groups on the prenyl side chain may be important.CONCLUSION:Our findings for the first time demonstrate that four caged xanthones induce apoptosis in CCA cells which is mediated through a mitochondriadependent signaling pathway. 关 键 词：Garcinia hanburyi Caged xanthones Human cholangiocarcinoma cell lines APOPTOSIS