Abstract:
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 apoptosis-inducing 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 mitochondria-dependent signaling pathway.
journal_name
World J Gastroenteroljournal_title
World journal of gastroenterologyauthors
Hahnvajanawong C,Boonyanugomol W,Nasomyon T,Loilome W,Namwat N,Anantachoke N,Tassaneeyakul W,Sripa B,Namwat W,Reutrakul Vdoi
10.3748/wjg.v16.i18.2235subject
Has Abstractpub_date
2010-05-14 00:00:00pages
2235-43issue
18eissn
1007-9327issn
2219-2840journal_volume
16pub_type
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