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

World Journal of Gastroenterology 2010年第18期16卷 2235-2243页

作者： Chariya Hahnvajanawong wongwarut boonyanugomol Tapanawan Nasomyon Watcharin Loilome Nisana Namwat Natthinee Anantachoke Wichittra Tassaneeyakul Banchob Sripa Wises Namwat Vichai Reutrakul Department of Microbiology Center of Excellence for Innovation in Chemistryand Liver Fluke and Cholangiocarcinoma Research CenterFaculty of MedicineKhon Kaen University Department of Biochemistry Faculty of MedicineKhon Kaen University Department of Pharmacognosy Faculty of PharmacyMahidol University Department of Pharmacology Faculty of MedicineKhon Kaen University Department of Pathology Faculty of MedicineKhon Kaen University Department of Chemistry and Center of Excellence for Innovation in ChemistryFaculty of ScienceMahidol University

AIM:To investigate the growth inhibitory mechanism of four caged xanthones from Garcinia hanburyi in cholangiocarcinoma(CCA) KKU-100 and KKU-M156 ***:Four caged xanthones,selected on the basis of their anticancer potency and chemical structure diversities(***,isomorellinol,forbesione and gambogic acid) were used in this *** inhibition of these caged xanthones was determined using the sulforhodamine B *** of apoptosis was assessed by observing cell morphology,ethidium bromide and acridine orange staining and DNA fragmentation *** of apoptotic-related gene and protein expressions were determined by a real-time reverse transcriptase polymerase chain reaction and Western blotting analysis,***: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 *** suppression by these compounds was due to apoptosis,as evidenced by the cell morphological changes,chromatin condensation,nuclear fragmentation,and DNA ladder *** 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 *** 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 ***:Our findings for the first time demonstrate that four caged xanthones induce apoptosis in

关键词： Garcinia hanburyi Caged xanthones Human cholangiocarcinoma cell lines Apoptosis

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